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A National Cross-sectional Study on Effects of Fluoride-safe Water Supply on the Prevalence of Fluorosis in China
ForJournal: peerBMJ Open review only Manuscript ID: bmjopen-2012-001564
Article Type: Research
Date Submitted by the Author: 27-May-2012
Complete List of Authors: Wang, Cheng; Harbin Medical University, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention Gao, Yanhui; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Wang, Wei; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Zhao, Lijun; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Zhang, Wei; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Han, Hepeng; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Shi, Yuxia; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Yu, Guangqian; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University http://bmjopen.bmj.com/ Sun, Dianjun; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University
Primary Subject Epidemiology Heading:
Secondary Subject Heading: Epidemiology, Public health
Keywords: EPIDEMIOLOGY, PUBLIC HEALTH, FLUOROSIS on September 23, 2021 by guest. Protected copyright.
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1 2 3 4 A National Cross-sectional Study on Effects of Fluoride-safe Water Supply 5 6 on the Prevalence of Fluorosis in China 7 8 Cheng Wang a, Yanhui Gao a, Wei Wang, Lijun Zhao, Wei Zhang, Hepeng Han, Yuxia Shi, 9
10 Guangqian Yu, Dianjun Sun * 11 Design A national cross sectional study in 1985 randomly selected villages in 27 provinces 12 13 (or cities and municipalities) in 5 geographic areas all over China. 14 15 For peer review only 16 All authors are in the Center for Endemic Disease Control, Chinese Center for Disease 17 18 Control and Prevention, Harbin Medical University; Key Lab of Etiologic Epidemiology, 19 20 Harbin Medical University, Education Bureau of Heilongjiang Province & Ministry of Health 21 (23618104), Harbin 150081, China. 22
23 24 a 25 Cheng Wang and Yanhui Gao contributed equally to this work. 26 27 28 Running title: A National Study on Effects of Fluoride safe Water Supply on Fluorosis 29 30 31 Email address of all authors: 32 33 Cheng Wang PhD: [email protected]
34 Yanhui Gao PhD: [email protected] http://bmjopen.bmj.com/ 35 36 Wei Wang BS: [email protected] 37 38 Lijun Zhao PhD: [email protected] 39 Wei Zhang PhD: [email protected] 40 41 Hepeng Han MD: [email protected] 42 43 Yuxia Shi MD: [email protected] on September 23, 2021 by guest. Protected copyright. 44 Guangqian Yu PhD: gq [email protected] 45 46 Dianjun Sun PhD: [email protected] 47 48 49 * Corresponding: Dianjun Sun 50 51 The Center for Endemic Disease Control, Chinese Center for Disease Control and 52 Prevention, Harbin Medical University; Key Lab of Etiologic Epidemiology, Harbin Medical 53 54 University, Ministry of Health & Education Bureau of Heilongjiang Province; 157 Baojian 55 56 Road, Nangang District, Harbin Medical University, Harbin, Heilongjiang Province 150081. 57 Telephone: +86 0451 86612695; fax: +86 0451 86676184; e mail: [email protected]. 58 59 1 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 Abstract 4 5 Objective To assess the effects of provided the fluoride safe drinking water for the prevention 6 7 and control of endemic fluorosis in China. 8 9 Design A national cross sectional study in China. 10 11 Setting In 1985 randomly selected villages in 27 provinces (or cities and municipalities) in 5 12 13 geographic areas all over China. 14 15 ParticipantsFor Involved 81 peer 786 children agedreview from 8 to 12 and 594only 698 adults aged over 16. 16 17 Main outcome measure The Prevalence of dental fluorosis and clinical skeletal fluorosis, the 18 fluoride concentrations in the drinking water in these study villages and in the urine of the 19 20 subjects. 21 22 Results The study shown that in the villages where the drinking water fluoride concentrations 23 24 were higher than the government standard of 1.2 mg/L, but no fluoride safe drinking water 25 26 supply scheme was provided (FNB areas), the prevalent rate and index of dental fluorosis in 27 28 children, and prevalent rate of clinical skeletal fluorosis in adults were all significantly higher 29 30 than those in the history endemic villages after the fluoride safe drinking water were provided 31 32 (FSB areas). The prevalent rate of dental fluorosis, the concentration of fluoride in urine and the 33 prevalent rate of clinical skeletal fluorosis were found increased with the increase of fluoride
34 http://bmjopen.bmj.com/ 35 concentration in drinking water, and there were significant positive correlations between these 36 37 indexes and fluoride concentration in drinking water in the FNB areas. While, the prevalent rate 38 39 of dental fluorosis and clinical skeletal fluorosis in different age groups and their degrees of 40 41 prevalence were significantly lower in the FSB areas than those in the FNB areas. 42 43 Conclusions The provision of fluoride safe drinking water supply schemes could have on September 23, 2021 by guest. Protected copyright. 44 45 significant effects on the prevention and control of dental fluorosis and skeletal fluorosis. The 46 47 study also indicated that the dental and skeletal fluorosis is still prevailing in the high fluoride 48 49 drinking water areas in China. 50 51 52 Key words: Drinking water; Fluorosis; Dental fluorosis; Clinical skeletal fluorosis 53 54 55 56 57 58 59 2 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Introduction 5 6 Fluoride is one of the very few chemicals that have been shown to cause significant health 7 8 9 effects in people through drinking water. Low fluoride in drinking water (less than 0.5 ppm) 10 11 can causes dental caries, lack of formation of dental enamel, and reduced bone 12 13 1,2 14 mineralization. In contrast, long term consumption of drinking water containing high fluoride 15 For peer review only 16 concentration (more than 1 ppm) could cause adverse health effects ranging from mild dental 17 18 19 fluorosis to crippling skeletal fluorosis depending on the fluoride level and period of 20 21 exposure.1,2 Fluorosis induced by exposing to high fluoride though drinking water is quite 22 23 24 widespread in many countries in the world, including Argentina, Brazil, Canada, China, Eritrea, 25 26 Ethiopia, Germany, India, Indonesia, Israel, Japan, Kenya, Mexico, Niger, Nigeria, Norway, 27 28 29 Pakistan, Saudi Arabia, Senegal, South Africa, Spain, Sri Lanka, Sudan, Thailand, Turkey, 30 31 Uganda, United Republic of Tanzania, and the United States of America.3 It is now becoming a 32 33 public health problem and an increasing disease burden in worldwide, 4 especially in the
34 http://bmjopen.bmj.com/ 35 36 developing countries, and, in particular China. In China, fluorosis from drinking water is a 37 38 39 major endemic disease. A nationwide screening of high fluoride ( > 1.2mg/L) in drinking water 40 41 in those villages where fluoride safe piped drinking water supply had or not provided was 42 43 on September 23, 2021 by guest. Protected copyright. 44 carried out from 2005 to 2007 in 231 175 villages in 27 provinces all over China. In those 45 46 villages where fluoride safe piped drinking water supply had been provided, water samples 47 48 49 were randomly taken from the pipelines to test fluoride concentrations in water. In those 50 51 villages where fluoride safe piped drinking water supply had not been provided, water samples 52 53 54 were randomly collected from wells located in the east, west, south, north, and center of the 55 56 villages. This investigation found that water fluoride concentration in wells or piped water 57 58 59 3 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 supplies was higher than the Chinese national standard of 1.2mg/L in 51 695 villages in the 27 5 6 provinces, where the population is more than 39 million. Most of these villages are located in 7 8 9 the geographic areas of Northeast, Northwest, and Central China. A total 47 057 fluoride safe 10 11 drinking water supply schemes covering 79 190 villages have been surveyed and the fluoride 12 13 14 concentration in 14.54 percent of these fluoride safe drinking water supply schemes exceeded 15 For peer review only 16 the Chinese national standard of 1.2 mg/L. Through this investigation, the endemic fluorosis 17 18 19 areas in these 27 provinces had been identified. 20 21 At present, most of the studies5 9 on endemic fluorosis caused by drinking water focused on 22 23 24 the correlation between fluoride levels in drinking water and in urine as well as the incidents of 25 26 dental fluorosis and skeletal fluorosis. A high correlation between fluorosis incidents and the 27
28 5 8 29 fluoride levels in drinking water has been found. However, with the exception of China, over 30 31 the past years, few reports from others countries have reported on the provision of fluoride safe 32 33 drinking water supply in the fluoride contaminated areas at large scale. In India, a report in
34 http://bmjopen.bmj.com/ 35 36 April 2011, 9 mentioned a de fluorination pilot project was installed at the level of community, 37 38 39 but finally the project came to a virtual collapse for failing to manage the project and bear the 40 41 high cost in the process of maintenance in this project. 42 43 on September 23, 2021 by guest. Protected copyright. 44 In China, since 1978, the fluoride safe drinking water supply schemes have been built to 45 46 provide fluoride safe drinking water to the population in the high fluoride areas and fluorosis 47 48 49 endemic areas. Through decades’ efforts of the Government, the fluoride concentrations in the 50 51 drinking water in many villages have been under control to meet the government standard. In 52 53 54 the basis of identified the endemic fluorosis areas in these 27 provinces in 2005 to 2007, with 55 56 funds provided by the Government, the present study was carried out in 2008 2009 to access 57 58 59 4 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 the prevalence of endemic fluorosis, and to evaluate the effects of providing fluoride safe 5 6 drinking water supply on the prevention and control of fluorosis in China. 7 8 9 Subjects and Methods 10 11 Fluoride-safe water supply schemes 12 13 14 For the provision of fluoride safe water supply to villages, two technical options were adopted: 15 For peer review only 16 (1) using the alternative low fluoride water sources that comply with the national standard (≤ 17 18 19 1.2 mg/l), and (2) de fluorination through the normal adsorption techniques with activated 20 21 alumina or electrodialysis method.10 Two scales of fluoride safe water supply schemes were 22 23 24 provided: (1) large centralized piped water supply systems that can provide more than 1000 25 26 cubic meter water per day or enough water for more than 10 000 persons daily, and (2) small 27 28 29 centralized piped water supply schemes that can provide water to the residents below the above 30 31 quantity. In the present study, the time of the centralized piped water supply schemes used 32 33 correctly were investigated, which were as the time of the switch from high fluoride to
34 http://bmjopen.bmj.com/ 35 36 fluoride safe water. 37 38 39 Study areas and contents 40 41 The present study evaluating the effects of providing fluoride safe drinking water supply on the 42 43 on September 23, 2021 by guest. Protected copyright. 44 prevention and control of fluorosis through accessing the prevalence of endemic fluorosis from 45 46 2008 2009 carried out in 231 175 selected villages in 27 provinces in 5 geographic areas all 47 48 49 over China, as presented in Figure 1, was based on outcomes of an early survey which aim was 50 51 to identify the whole endemic fluorosis areas in china, conducted in 2005 2007, on high 52 53 54 fluoride in drinking water areas that included the previous endemic areas where fluoride safe 55 56 water supply schemes had been build with the current fluoride level in water below 1.2 mg/l. 57 58 59 5 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 The study villages were divided into 3 categories for the investigation. These are: (1) villages 5 6 where water fluoride concentration is higher than 1.2mg/Lwith no fluoride safe water supply 7 8 9 scheme provided, and villages in mild endemic fluorosis areas with fluoride safe water supply 10 11 scheme provided; (2) villages where drinking water fluoride concentration is higher than 12 13 14 2.0mg/L with no fluoride safe water supply scheme provided, and villages in the moderate 15 For peer review only 16 endemic fluorosis areas with fluoride safe water supply scheme provided; and (3) villages 17 18 19 where drinking water fluoride concentration is higher than 4.0mg/L with no fluoride safe water 20 21 supply scheme provided, and villages in the severe endemic fluorosis areas with fluoride safe 22 23 24 water supply schemes provided. 25 26 According to the proportion of 4% in every category, 1985 study villages were selected 27 28 29 randomly for this study with random numbers generated by SPSS (version 13.01S; Beijing 30 31 Stats Data Mining Co. Ltd, Beijing, China), which was carried out in 2008 ~ 2009. In these 32 33 selected villages, the prevalence of dental fluorosis was assessed in all children aged from 8 to
34 http://bmjopen.bmj.com/ 35 36 12. In every village, 6 children in every age group from 8 to 12 were randomly selected to test 37 38 39 the fluoride concentration in their urines, and the total number of identified children in each 40 41 village would be 30. If the total numbers of children in each village are less than 30 or 42 43 on September 23, 2021 by guest. Protected copyright. 44 there were less than six children in each age group, all children’s urine fluoride concentrations 45 46 were to be tested. For the test of urine fluoride level in adults, 20 adults were randomly selected 47 48 49 among adult age group over 20 with the ratio male to female at 50 to 50. The urine fluoride in 50 51 adults was tested in 2009 and not in 2008. The prevalence of clinical skeletal fluorosis was 52 53 54 investigated in all persons over 16 years of age (denoted as adults). The study protocol was 55 56 approved by the Ethics Committee of the Harbin Medical University. 57 58 59 6 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Assessment of fluorosis endemic areas 5 6 Endemic fluorosis areas were assessed in the following areas in this study. 7 8 9 The areas where water fluoride concentration is high than 1 2 mg/L, are covered within the 10 11 endemic fluorosis areas, in which, and they were divided into three classes according to the 12 13 14 prevalence of fluorosis: (1) mild endemic fluorosis areas: in these areas where the prevalent rate 15 For peer review only 16 of dental fluorosis is moderate, and the severe degrees in the native born residents of 8 to 12 17 18
19 years old children is equal to, or less than 20%, or there are mild skeletal fluorosis patients but 20 21 no moderate skeletal fluorosis patients; (2) moderate endemic fluorosis areas: in these areas 22 23 24 where the prevalent rate of dental fluorosis is moderate, and the severe degrees in the 25 26 native born residents of 8 to 12 years old children is in the range of 20% ~ 40%, or there are 27 28 29 skeletal fluorosis patients in moderate and severe degrees, but the prevalence of severe skeletal 30 31 fluorosis is equal to, or less than 2%; and (3) severe endemic areas: in these areas where the 32 33 prevalent rate of dental fluorosis is moderate, and the severe degrees in the native born
34 http://bmjopen.bmj.com/ 35 36 residents of 8 to 12 years old children is higher than 40 %, or the prevalent rate of severe 37 38 39 skeletal fluorosis is more than 2%. 40 41 Determination of fluoride in drinking water and urine and the diagnosis of dental fluorosis 42 43 on September 23, 2021 by guest. Protected copyright. 44 and skeletal fluorosis 45 46 The water fluoride concentrations in two different areas were tested: (1) in areas where 47 48 49 fluoride safe water supply schemes had been provided (FSB villages); and (2) in areas where 50 51 no fluoride safe water supply scheme is provided (FNB villages). In the FNB villages, 5 water 52 53 54 samples were randomly collected in the wells located in the east, west, south, north, and center 55 56 of each village, which represent the water quality of the whole village, and the concentrations 57 58 59 7 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 of fluoride were tested, and the mean value was calculated. In the FSB villages, 3 water 5 6 samples from the pipeline of each fluoride safe water supply scheme were randomly collected 7 8 9 and the fluoride concentrations were tested, and the mean value was calculated. The urina 10 11 sanguinis of the study subjects were collected in the morning for testing. The concentrations of 12 13 14 fluoride in drinking water samples and urine samples are analyzed with ion selective electrode 15 For peer review only 16 methods (WS/T106 1999 11 for water and WS/T89 1996 12 for urine). Dental fluorosis was 17 18 13 19 diagnosed using Dean’s method recommended by WHO. An individual’s fluorosis condition 20 21 is based on the most severe form of fluorosis found on two or more teeth. An individual’s dental 22 23 24 status can be classified into six parts: normal, questionable, very mild, mild, moderate and 25 26 severe. The clinical diagnosis of skeletal fluorosis followed the Diagnostic Criteria of Endemic 27
28 14 29 Skeletal Fluorosis (WS 192 2008) . An individual’s skeletal fluorosis status is based on the 30 31 severe form of persistent rest pain of Neck, waist and the large joints of limb, severe dyskinesia, 32 33 limb deformity, and even paralysis, and can be classified into three parts: mild, moderate and
34 http://bmjopen.bmj.com/ 35 36 severe. 37 38 39 Quality Control of project implementation 40 41 This study was carried out by the Centre for Endemic Disease Control, Chinese Centre for 42 43 on September 23, 2021 by guest. Protected copyright. 44 Disease Control and Prevention led by the Ministry of Health. The study was planned through 45 46 discussion with experts in the fields of Chinese endemic and epidemic diseases, and the Quality 47 48 49 Control of project implementation was carried out in several aspects including: (1) as per the 50 51 requirements in the Government guidelines on "the project management scheme" and "the 52 53 54 project technical solutions" of national drinking water fluorosis survey, all provinces, 55 56 autonomous regions and municipalities were requested to develop their own respective 57 58 59 8 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 implementation plans in accordance with the local conditions, and to carry out this study; (2)the 5 6 provincial institutions for disease prevention and control selected survey villages in accordance 7 8 9 with the principles of randomization, and then sent the survey task to the concerned counties 10 11 where the selected villages belonged. The institutions for disease prevention and control in the 12 13 14 respective concerned counties are then responsible for the survey in the selected villages; (3) 15 For peer review only 16 the concerned technical workers for the analysis of fluoride concentrations in water and urine, 17 18 19 diagnosis of dental fluorosis and clinical skeletal fluorosis, and data entry were all trained in 20 21 provincial institutions, and the concerned staffs at provincial levels were trained by the national 22 23 24 experts in the national center of endemic disease to ensure that uniform methods and standard 25 26 techniques are applied in the investigation for ensuring the accuracy of illness diagnosis and 27 28 29 reporting of data in this investigation; (4) the provincial institutions were responsible for 30 31 quality control/assessment on the analysis of fluoride concentrations in water and urine samples 32 33 in all concerned county level laboratories, and the external quality control samples were from
34 http://bmjopen.bmj.com/ 35 36 the Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention. 37 38 39 The laboratories taking up the test of fluoride concentrations in water and urine samples are 40 41 permitted to carry out the analysis tasks uniformly arranged by provincial agencies if they 42 43 on September 23, 2021 by guest. Protected copyright. 44 passed the assessment by external quality control; (5) when the provincial institutions 45 46 completed the first supervision and inspection on assessment conducted in project villages, and 47 48 49 if some problems were found/detected, corrections should be made in due course for further 50 51 project implementation. At the end of the project, the consistency of project implementation, 52 53 54 the rationality of sample collections and sampling methods, as well as the accuracy of the 55 56 analysis technologies and disease diagnostic were all needed to be assessed. 57 58 59 9 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Statistical analysis 5 6 Statistical analysis of the results obtained was carried out in all FSB and FNB villages 7 8 9 respectively. In FSB areas, the prevalence of fluorosis was compared in three stages, based on 10 11 the length of time in which the fluoride safe water supply schemes were provided, say, in equal 12 13 14 or less than 5 years, in between 5 to10 years and more than 10 years. In FNB areas (the FSB 15 For peer review only 16 villages where fluoride concentration in water supply schemes is higher than 1.2 mg/L are 17 18 19 considered as fluoride safe water supply non provided areas), the prevalence of fluorosis was 20 21 compared according to the fluoride concentrations in drinking water, i.e. in between 22 23 24 1.2~2.0mg/l, 2.0~4.0 mg/l, and higher than 4.0 mg/l. Statistical analyses were carried out using 25 26 SPSS. Data were presented as mean ± standard deviation (SD) or M estimators by Andrew with 27 28 29 inter quartile range as appropriate. Data that were not normally distributed, as determined with 30 31 the Kolmogorov Smirnov test, were logarithmically transformed to obtain near normality 32 33 before analysis. Chi square test was used to compare categorical variables. Bivariate
34 http://bmjopen.bmj.com/ 35 36 Correlations with spearman was used to analyze the correlation between variables. All P values 37 38 39 are 2 tailed and a P value < 0.05 was considered significant for all statistical analyses in this 40 41 study. 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 Results 47 48 49 In the FSB and FNB areas, 1404 and 581 villages were selected, respectively. Total 676 484 50 51 study subjects were investigated including 81 786 children and 594 698 adults. The prevalence 52 53 54 of dental fluorosis was investigated in 1876 villages covering 1318 FNB villages and 558 FSB 55 56 villages. The prevalence of clinical skeletal fluorosis was investigated in 1622 villages 57 58 59 10 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 consisting of 1152 FNB villages and 470 FSB villages respectively (In some villages, only 5 6 dental fluorosis and/or clinical skeletal fluorosis were surveyed as presented in Table 1 and 2. 7 8 9 The prevalence of dental fluorosis and clinical skeletal fluorosis was compared between FSB 10 11 and FNB areas. The photographs taken in the surveyed villages represented the patients 12 13 14 suffering from dental fluorosis and skeletal fluorosis (Figure 2). 15 For peer review only 16 Comparison of the prevalence of dental fluorosis, dental fluorosis index, fluoride 17 18 19 Concentrations in drinking-water and urine between the FNB and FSB areas 20 21 Children aged 8 to 12 including 54 855 in FNB areas and 26 931 in FSB villages were 22 23 24 investigated. The prevalence of dental fluorosis, dental fluorosis index, and fluoride 25 26 concentration in urine and in drinking water were significant lower in FSB areas than FNB 27 28 29 areas (Table 1). Prevalence of dental fluorosis in different ages and its prevalent degrees, 30 31 namely the very mild, mild, moderate and severe were all significantly lower in FSB areas 32 33 than FNB areas (Table 3).
34 http://bmjopen.bmj.com/ 35 36 Relationships between the prevalent rate of dental fluorosis, dental fluorosis index, fluoride 37 38 39 concentrations in urine and in drinking-water in FNB areas, and the period of the 40 41 fluoride-safe water supply provided in FSB areas 42 43 on September 23, 2021 by guest. Protected copyright. 44 The prevalent rate of dental fluorosis increased significantly with the increase of water fluoride 45 46 concentration in FNB areas. The prevalent rates of dental fluorosis were 40.82%, 55.06% and 47 48 49 67.20% in these areas where fluoride concentration in drinking water was 1.2~2.0mg/l, 2.0~4.0 50 51 mg/l, and > 4.0mg/l, respectively as shown in Figure 3, A. Significant positive correlation 52 53 54 between the prevalent rate of dental fluorosis and fluoride concentrations in drinking water (R 55 56 = 0.33, P < 0.001) is presented in Figure 4, A. The prevalent rate of dental fluorosis decreased 57 58 59 11 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 with the increase of length of time of the availability of fluoride safe water in the FSB areas. 5 6 The prevalent rates of dental fluorosis were 24.54%, 21.35% and 13.9%, respectively, in the 7 8 9 FSB villages where fluoride safe water supply schemes were provided for equal to or more than 10 11 5 years, between 5~10 years and more than 10 years respectively. And the prevalent rate of 12 13 14 dental fluorosis in the FSB areas where the availability of fluoride safe water supply less than 5 15 For peer review only 16 years (24.54%) was lower than that in the areas where fluoride concentration between 1.2~2.0 17 18 19 mg/l in FNB areas (the prevalent rate of dental fluorosis is lower than 30 percent, which is the 20 21 standard could be thought as un prevalence for the dental fluorosis in China. (Figure 3. A). 22 23 24 The dental fluorosis index and fluoride concentration in urine increased significantly with the 25 26 increase of fluoride concentration in drinking water in the FNB areas. The dental fluorosis 27 28 29 indices were 0.86, 1.17 and 1.53 and fluoride concentration in urine were 1.97 (1.21, 3.00), 30 31 2.53(1.50, 4.02), 3.41(2.12, 5.29) respectively in these FNB areas where ranges of fluoride 32 33 concentration in drinking water were 1.2~2.0mg/L, 2.0~4.0 mg/L, and > 4 0mg/L. And there
34 http://bmjopen.bmj.com/ 35 36 was a significant positive correlation between dental fluorosis index (R = 0.34, P < 0.001), 37 38 39 fluoride concentration (R = 0.43, P < 0.001) in urine and fluoride concentration in 40 41 drinking water as presented in Figure 4, B and C. In the FSB areas, the fluoride concentration 42 43 on September 23, 2021 by guest. Protected copyright. 44 in urine was significantly lower in villages where fluoride safe drinking water supply had been 45 46 provided for more than 5 years compared to that of less than 5 years. The fluoride concentration 47 48 49 in urine were 1.00(0.61, 1.89), 0.83(0.5, 1.36) and 0.85(0.52, 1.33) respectively in those areas 50 51 where fluoride safe water supply schemes had been provided for less than 5 years, between 5 to 52 53 54 10 years and more than 10 years. And the levels of urinary fluoride and dental fluorosis index 55 56 [1.00(0.61, 1.89) and 0.53] in the FSB areas where the availability of fluoride safe water 57 58 59 12 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 supply less than 5 years were lower than that in the areas where fluoride concentration between 5 6 1.2~2.0 mg/l in FNB areas as illustrating in Figure 3. B. 7 8 9 Prevalent rate of dental fluorosis in 5 geographic areas in China 10 11 Prevalent rates of dental fluorosis in FNB areas were significantly higher than that in FSB areas 12 13 14 in 5 geographic parts in China as presented in Table 2. 15 For peer review only 16 Comparison of the prevalent rate of clinical skeletal fluorosis and the fluoride concentration 17 18 19 in urine between the FNB and FSB areas 20 21 Adults aged more than 16 including 406 298 in FNB areas and 188 400 in FSB villages were 22 23 24 investiged. 25 26 The prevalence rate of clinical skeletal fluorosis and the fluoride concentration in urine and 27 28 29 in drinking water were significant lower in FSB areas than FNB areas as presented in Table 1. 30 31 Prevalent rate of clinical skeletal fluorosis in different age groups and its degrees of prevalence, 32 33 i.e. very mild, moderate and severe were all significantly lower in FSB areas compared with
34 http://bmjopen.bmj.com/ 35 36 FNB areas as illustrated in Table 3. 37 38 39 Relationships between the prevalent rate of clinical skeletal fluorosis, fluoride 40 41 concentrations in urine and in drinking-water in FNB areas and the length of time of 42 43 on September 23, 2021 by guest. Protected copyright. 44 fluoride-safe drinking water provision in FSB areas 45 46 The prevalent rate of clinical skeletal fluorosis increased significantly with the increase of 47 48 49 fluoride concentration in drinking water in the FNB areas. As presented in Figure 5, A, the 50 51 prevalent rate of clinical skeletal fluorosis increased (7.28%, 11.54% and 22.64%) with the 52 53 54 increase of fluoride concentrations in drinking water (1.2~2.0mg/l, 2.0~4.0 mg/l, and > 4.0mg/l) 55 56 respectively. And there was a significant positive correlation between the prevalent rate of 57 58 59 13 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 clinical skeletal fluorosis and fluoride concentration in drinking water (R = 0.20, P < 0.001) as 5 6 illustrated in Figure 4, D. In the FSB areas, the prevalence rate of clinical skeletal fluorosis 7 8 9 increased slightly and then subsequently decreased as the period of providing the fluoride safe 10 11 drinking water supply continuing to more than 10 years, still its value was lower than that in the 12 13 14 FNB areas where the drinking water fluoride concentration between 1.2~2.0 mg/l as shown in 15 For peer review only 16 Figure 5. A. 17 18 19 The fluoride concentrations in urine were found increased significantly with the increase of 20 21 fluoride concentrations in drinking water. Fluoride concentrations in urine were 1.99(1.30, 22 23 24 3.20), 2.97(1.73, 4.83), 3.77(2.17, 6.79) in areas where fluoride concentrations in drinking 25 26 water were 1.2~2.0mg/l, 2.0~4.0 mg/l, and > 4.0mg/l, respectively as illustrated in Figure 5. A. 27 28 29 Positive correlation between urine fluoride concentrations in adults’ and fluoride concentration 30 31 in drinking water (R = 0.42, P < 0.001) is presented in Figure 4. E. Urine fluoride 32 33 concentrations remains unchanged in FSB areas in longer period of available fluoride safe
34 http://bmjopen.bmj.com/ 35 36 drinking water supply, but it is lower than those in the FNB areas where drinking water fluoride 37 38 39 concentration is between 1.2 2.0 mg/l as shown in Figure 5. B. 40 41 Prevalent rate of clinical skeletal fluorosis in 5 geographic areas in China 42 43 on September 23, 2021 by guest. Protected copyright. 44 Prevalent rates of clinical skeletal fluorosis in FNB areas were significantly higher than that in 45 46 FSB areas in 5 geographic areas in China as presented in Table 2. 47 48 49 Discussion 50 51 Our study showed that provision of fluoride safe drinking water supply within the 52 53 54 government standard of 1.2 mg/l have significant effects on the control of dental fluorosis and 55 56 skeletal fluorosis, and decreasing fluoride concentrations in urine in the areas of high fluoride 57 58 59 14 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 in drinking water. Besides, this study also provided a scientific basis for assessing the 5 6 prevalence of fluorosis from drinking water. The present study also indicated that the prevalent 7 8 9 rates of dental fluorosis in children aged 8 ~ 12 and skeletal fluorosis in adults were 50.44 10 11 percent and 10.81 percent respectively in FNB areas (the FNB areas covered the villages in the 12 13 14 provinces where no fluoride safe drinking water supply is provided, and the villages where the 15 For peer review only 16 water fluoride concentrations in drinking water exceeding the government standard, and the 17 18 19 fluoride safe drinking water supply schemes were provided). Based on the outcomes of this 20 21 study, it is estimated that 1.35 million of children aged from 8 to 12 having dental fluorosis and 22 23 24 3.15 million adults in the age groups of more than 16 years suffering from both dental fluorosis 25 26 and skeletal fluorosis in FNB areas and in some FSB areas where the fluoride level in drinking 27 28 29 water exceeded the government standard. These fluorosis patients were mainly distributed in 30 31 the northeast, northwest and central geographic parts in China. However, in these geographic 32 33 areas, the endemic fluorosis is relatively more severe in the provinces of Heilongjiang, Inner
34 http://bmjopen.bmj.com/ 35 36 Mongolia, Xinjiang, Gansu, Tianjin, Hebei, Henan, Jiangsu, Shandong, and Anhui than in other 37 38 39 provinces. These provinces would be the priority areas where the fluoride safe water supply 40 41 schemes should be provided in the future. 42 43 on September 23, 2021 by guest. Protected copyright. 44 The relationships between levels of drinking water fluoride and urine fluoride, dental 45 46 fluorosis and skeletal fluorosis have been reported in studies 15 19 in Japan, Indian, Germany 47 48 49 and South Africa. In their studies, it reported that there were significantly higher prevalence 50 51 rates of dental fluorosis 15 18, skeletal fluorosis 19, 20 and higher urine fluoride concentrations 21 52 53 54 in areas having high fluoride concentrations than low fluoride concentrations in drinking water, 55 56 which were consistent with the results in the FNB areas in the present study. Excessive intake 57 58 59 15 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 of fluoride can cause the dental fluorosis and skeletal fluorosis, even with severe dyskinesia, 5 6 limb deformity and even paralysis.14, 22, 23, 24 In addition, fluoride can damage the digestive, 7 8 25 9 nervous, immune, and urinary systems. Therefore, disruption or damage of these systems can 10 11 have a wide range of effects on the body. Moreover, the fluoride can also damage the 12 13 26, 27 14 intelligence of children. 15 For peer review only 16 Based on the severe harmful effects of fluorosis to human beings, some measures should be 17 18 19 taken to control the occurrence and progress of fluorosis. First, the effects of pharmaceutical 20 21 intervention on dental fluorosis and skeletal fluorosis could not let us feel satisfied enough, 28 22 23 24 and severe patients finally need to carry out surgery, which result was also indeterminate; 25 26 second, Because the bioavailability of fluoride is generally reduced in humans when consumed 27
28 29 30 29 with milk (decreased to 70%) or a calcium (decreased to 60%) rich diet, it has been highly 30 31 recommended that the inhabitants of fluoride contaminated areas should incorporate 32 33 calcium rich foods in their routine diet. But such measures could not fundamentally solve such
34 http://bmjopen.bmj.com/ 35 36 a problem, and it could not also be implemented in poverty areas. Therefore, changing the 37 38 39 drinking water source used for the inhabitants living in fluoride contaminated areas may be an 40 41 appropriate way to prevent and control the fluorosis. In 1995, a study by Boyle et al 19 in Gasp 42 43 on September 23, 2021 by guest. Protected copyright. 44 region, Quebec of Canada mentioned the well drilling should be in different deeps according to 45 46 the F levels in different groundwater layers through studying the relationships between the 47 48 49 prevalence of fluorosis and F levels in groundwater in different areas. And Boyle indicated that 50 51 Hydrogeochemists, hydrologists, health officials, and environmental regulators should work 52 53 54 closely together in order to efficiently eradicate the risk of skeletal fluorosis from drinking 55 56 waters associated with geological environments where such risks exist. Although some advices 57 58 59 16 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 5 8 4 were proposed, however, with the exception of China, there were few relative reports in 5 6 others countries on providing large scale fluoride safe water in the past many years. These 7 8 5 8 9 studies reported the fluoride concentration in drinking water and urine, and the prevalent 10 11 rate of dental fluorosis or skeletal fluorosis after the fluoride safe drinking water supply 12 13 14 schemes have been provided. However, most of studies were carried out in one or several 15 For peer review only 16 provinces not in the national scale, and the selected villages were seldom than the present 17 18 19 study. In addition, most of studies only reported several values of the fluoride concentration in 20 21 drinking water and/or urine, and/or the prevalent rate of dental fluorosis and/or skeletal 22 23 24 fluorosis, not including all of them. Furthermore, these above values were not compared 25 26 between FNB and FSB areas, and the effects of fluoride safe water supply on the prevalence 27 28 29 of fluorosis could not been evaluated. 30 31 In China, the fluoride safe drinking water supply schemes have been provided in high water 32 33 fluoride areas for many years. Through years of cooperation between various agencies, such as
34 http://bmjopen.bmj.com/ 35 36 water resources, geology and health, rich experience has been accumulated as basis on the 37 38 39 implementation of this study. During the study period, however, some issues were observed 40 41 such as problems of difficulty in locating low fluoride level of drinking water sources and/or 42 43 on September 23, 2021 by guest. Protected copyright. 44 proper lining of wells after those wells have been drilled and proper maintenance, supervision 45 46 and operation of the fluoride safe drinking water supply schemes that have been provided. In 47 48 49 addition, during this study, some of the fluoride safe drinking water supply schemes were 50 51 found to have fluoride concentration more than 1.2 mg/l. As such, these ‘fluoride safe’ drinking 52 53 54 water supply schemes in fact are no longer ‘fluoride safe’ at all. In fact, these water schemes are 55 56 providing ‘non fluoride safe’ drinking water to the population covered as such. It is harmful to 57 58 59 17 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 the residents’ health by inducing dental fluorosis and skeletal fluorosis. The fact was that prior 5 6 to the fluoride safe water supply schemes were provided, the local residents were using water 7 8 9 from their own tube wells with various depths, and not all tube wells have high fluoride 10 11 concentration (depending on the geological formation). Therefore, it is extremely important to 12 13 14 strength the monitoring of the fluoride level in all fluoride safe drinking water supply schemes 15 For peer review only 16 starting from identifying the water sources to operation and maintenance to ensure that the 17 18 19 fluoride level in these fluoride safe water schemes is within the government standard and to 20 21 carry out the surveillance of the prevalence of fluorosis for cross checking of the fluoride 22 23 24 concentrations in the fluoride safe drinking water supply schemes for long term sustainability 25 26 of supplying the fluoride safe drinking water in those areas where the fluoride safe drinking 27 28 29 water supply schemes had been provided for the prevention and control of endemic fluorosis. 30 31 Conclusions 32 33 In summary, the fluoride safe drinking water supply schemes had been provided in various
34 http://bmjopen.bmj.com/ 35 localities in various provinces in China for decades. The study found that by providing 36 37 38 alternative fluoride safe water supply have significant effects on controlling the occurrence and 39 40 progress of dental fluorosis and skeletal fluorosis. The study also indicated that the dental and 41 42 43 skeletal fluorosis is still prevailing in the high fluoride drinking water areas in China. To control on September 23, 2021 by guest. Protected copyright. 44 45 and prevent the continuous spreading of endemic fluorosis in China, it is proposed that 46 47 48 government’s effort be given to provide the fluoride safe drinking water supply schemes in all 49 50 high fluoride drinking water areas in China with proper operation and maintenance of these 51 52 53 fluoride safe water supply schemes provided. 54 55 Acknowledgements 56 57 58 We are grateful to the generous support by many researchers and medical professionals from 59 18 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 the various Centers for Endemic Disease Control in the 27 provinces, autonomous regions and 5 6 municipalities and for their continuous efforts and collaboration during this study. We wish to 7 8 9 acknowledge the close cooperation of many fluorosis patients who allowed us to do the 10 11 examination and checking up for this study. 12 13 14 Contributors 15 For peer review only 16 DJ Sun takes responsibility for obtaining the funding, the design and conduct of the study, 17 18 19 interpretation of the data, and writing of this manuscript. C Wang and YH Gao take 20 21 responsibility for the interpretation, analysis of the data, and writing of this manuscript. W 22 23 24 Wang, Lijun Zhao, W Zhang, YX Shi, HP Han, and GQ Yu take responsibility for the data 25 26 collection and management. 27 28 Funding: This work was supported by the Chinese government for Endemic Disease Control 29 in 2008 ~ 2009 years. 30 31 Conflicts of interest 32 33 We declare that we have no conflicts of interest.
34 http://bmjopen.bmj.com/ 35 36 Exclusive licence 37 38 The Corresponding Author has the right to grant on behalf of all authors and does grant on 39 40 behalf of all authors, an exclusive licence (or non exclusive for government employees) on a 41 42 worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if 43 on September 23, 2021 by guest. Protected copyright. 44 accepted) to be published in BMJ editions and any other BMJPGL products and sublicences 45 to exploit all subsidiary rights, as set out in our licence. 46 47 48 49 50 51 52 53 54 55
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1 2 3 4 References 5 6 1 World Health Organization. Guidelines for drinking water quality. Recommendations, 7 8 9 vol 1. http://www.who.int/water_sanitation_health/dwq/gdwq3rev/en/ (accessed 10 10 11 November 2011). 12 13 14 2 Jha SK, Mishra VK, Sharma DK, Damodaran T. Fluoride in the environment and its 15 For peer review only 16 metabolism in humans. Rev Environ Contam Toxicol 2011; 211:121 142. 17 18 19 3 World Health Organization. Fluoride in Drinking water. 20 21 http://www.who.int/water_sanitation_health/publications/fluoride_drinking_water/en/ind 22 23 24 ex.html (accessed 10 November 2011). 25 26 4 Fewtrell L, Smith S, Kay D, Bartram J. An attempt to estimate the global burden of 27 28 29 disease due to fluoride in drinking water. J Water Health 2006; 4:533 542. 30 31 5 Zhu C, Bai G, Liu X, Li Y. Screening high fluoride and high arsenic drinking waters and 32 33 surveying endemic fluorosis and arsenism in Shaanxi province in western China. Water
34 http://bmjopen.bmj.com/ 35 36 Res 2006; 40:3015 3022. 37 38 39 6 Liang C. Evaluation on the effects of water defluoridation measures in China. Journal of 40 41 Hygiene Research 1998; 27:16 28. [Article in Chinese] 42 43 on September 23, 2021 by guest. Protected copyright. 44 7 Wu J, Zhang J, Chen Z, Du G. Survey on children's dental fluorosis and fluoride content 45 46 in urine after defluridation to improve drinking water. Journal of Hygiene Research 2000; 47 48 49 29:218 220. [Article in Chinese] 50 51 8 Collaboration Group of National Endemic Fluorosis Surveillance. Report on the 52 53 54 surveillance of endemic fluorosis of drinking water type in China in 2005 and 2006. 55 56 Chinese Journal of Endemiology 2009; 28:175 180. 57 58 59 20 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 21 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 9 Bikash KP and Bikash Rath. The Raipali experience. 2011; 5 6 http://www.rcdcindia.org/raipalli.pdf. 7 8 9 10 Mohapatra M, Anand S, Mishra BK, Giles DE, Singh P. Review of fluoride removal from 10 11 drinking water. J Environ Manage 2009; 91:67 77. 12 13 14 11 Ministry of Health of the People's Republic of China, Method for Determination of 15 For peer review only 16 Fluoride in Drinking Water of Endemic Fluorosis Areas (WS/T 106 1999), 1999. 17 18 19 12 Ministry of Health of the People's Republic of China, Determination of Fluoride in 20 21 Urine ion Selective Electrode Method (WS/T 89 1996), 1996. 22 23 24 13 Dean HT. The investigation of physiological effects by the epidemiological method. In: 25 26 Moulton FR, ed. Fluorine and dental health. Washington, DC: American Association for 27 28 29 the Advancement of Science. 1942:23 31. 30 31 14 Ministry of Health of the People's Republic of China, Diagnostic Criteria of Endemic 32 33 Skeletal Fluorosis (WS 192 2008), 2008.
34 http://bmjopen.bmj.com/ 35 36 http://www.wwwstandard.cn/index.php?doc view 22507.html. 37 38 39 15 Fantong WY, Satake H, Ayonghe SN, et al. Geochemical provenance and spatial 40 41 distribution of fluoride in groundwater of Mayo Tsanaga River Basin, Far North Region, 42 43 on September 23, 2021 by guest. Protected copyright. 44 Cameroon: implications for incidence of fluorosis and optimal consumption dose. 45 46 Environ Geochem Health 2010; 32:147 163. 47 48 49 16 Yadav JP, Lata S, Kataria SK, Kumar S. Fluoride distribution in groundwater and survey 50 51 of dental fluorosis among school children in the villages of the Jhajjar District of Haryana, 52 53 54 India. Environ Geochem Health 2009;31:431 438. 55 56 57 58 59 21 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 22 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 17 Shomar B, Müller G, Yahya A, Askar S, Sansur R. Fluorides in groundwater, soil and 5 6 infused black tea and the occurrence of dental fluorosis among school children of the 7 8 9 Gaza strip. J Water Health 2004; 2: 23 35. 10 11 18 Grobleri SR, Louw AJ, van Kotze TJ. Dental fluorosis and caries experience in relation to 12 13 14 three different drinking water fluoride levels in South Africa. Int J Paediatr Dent 2001;11: 15 For peer review only 16 372 379. 17 18 19 19 Boyle DR, Chagnon M. An incidence of skeletal fluorosis associated with groundwaters 20 21 of the maritime carboniferous basin, Gasp region, Quebec, Canada. Environ Geochem 22 23 24 Hlth 1995; 17: 5 12 25 26 20 Choubisa SL, Choubisa L, Choubisa D. Osteo dental fluorosis in relation to age and sex 27 28 29 in tribal districts of Rajasthan, India. J Environ Sci Eng 2010; 52:199 204. 30 31 21 Yadav JP, Lata S. Urinary fluoride levels and prevalence of dental fluorosis in children of 32 33 Jhajjar District, Haryana. Indian J Med Sci 2003;57: 394 399
34 http://bmjopen.bmj.com/ 35 36 22 Kumar H, Boban M, Tiwari M. Skeletal fluorosis causing high cervical myelopathy. J 37 38 39 Clin Neurosci 2009; 16:828 830. 40 41 23 Shashi A, Kumar M, Bhardwaj. Incidence of skeletal deformities in endemic fluorosis. 42 43 on September 23, 2021 by guest. Protected copyright. 44 Trop Doct 2008; 38:231 233. 45 46 24 Everett ET. Fluoride's effects on the formation of teeth and bones, and the influence of 47 48 49 genetics. J Dent Res 2011; 90: 552 560. 50 51 25 National Research Council, “Fluoride in Drinking Water: A Scientific Review of EPA’s 52 53 54 Standards” 2006; http://www.nap.edu/catalog.php?record_id=11571. Accessed 55 56 December 5, 2011. 57 58 59 22 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 23 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 26 Ding YP, Gao YH, Sun HX, et al. The relationships between low levels of urine fluoride 5 6 on children’s intelligence,dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner 7 8 9 Mongolia, China. J. Hazard. Mater 2011; 186: 1942 1946. 10 11 27 Wang SX, Wang ZH, Cheng XT, et al. Arsenic and fluoride exposure in drinking water: 12 13 14 children's IQ and growth in Shanyin county, Shanxi province, China. Environ Health 15 For peer review only 16 Persp 2007; 115: 643 647. 17 18 19 28 Sang ZC, Zhou W, Zhang ZJ, et al. X ray analysis on 114 patients with moderate 20 21 endemic skeletal fluorosis by treatment of Guo's Chinese herbal. Zhongguo Gu Shang 22 23 24 2010; 23: 379 382. [Article in Chinese] 25 26 29 Ekstrand J, Ehrnebo M. Influence of milk products on fluoride bioavailability in man. 27 28 29 Eur J Clin Pharmacol 1979; 16: 211–215. 30 31 30 Shulman ER, Vallejo M. Effect of gastric contents on the bioavailability of fluoride in 32 33 humans. Pediatr Dent 1990; 12:237–240
34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 on September 23, 2021 by guest. Protected copyright. 43 44 45 46 47 48 49 50 51 52 53 54 55
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1 2 3 4 Figure legends 5 6 Figure 1. Locations of 27 provinces in the 5 geographic areas in China. 7 8 Figure 2. A: a girl with dental fluorosis; B: an adult with skeletal fluorosis, and photos taken 9 10 during the investigation. 11 12 Figure 3. A: Relationships between prevalent rate of dental fluorosis and various fluoride 13 14 concentrations in the drinking water in FNB areas, and the period of fluoride safe drinking 15 For peer review only 16 water supply schemes built in FSB areas. B: Relationships between the index of dental 17 18 fluorosis and urine fluoride concentrations in children, and the fluoride concentration in 19 20 drinking water in FNB areas, and the period of fluoride safe drinking water supply schemes 21 22 built in FSB areas. *: comparing with that in the areas with fluoride concentration was 23 24 1.2~2.0 mg/L in drinking water. **: comparing with that in the areas with fluoride 25 26 concentration was 2.0~4.0 mg/L in drinking water. †: comparing with that of fluoride safe 27 28 water supply projects built for ≤ 5 years. ††: comparing with that of fluoride safe water 29 30 supply projects built for 5~10 years. All P values were < 0.001. 31 32 Figure 4 Correlation between fluoride concentrations in drinking water and variables 33 including A: prevalence of dental fluorosis, B: Dental fluorosis index, C: Fluoride 34 http://bmjopen.bmj.com/ 35 36 concentration in children urine, D: Prevalence rate of skeletal fluorosis, and E: Fluoride 37 38 concentrition in adult urine (mg/L). All P values were < 0.001. 39 40 Figure 5 A: Relationships between prevalent rate of clinical skeletal fluorosis and fluoride 41 42 concentration in drinking water in FNB areas, as well as the period of fluoride safe water 43 on September 23, 2021 by guest. Protected copyright. 44 supply schemes built in FSB areas; B: the relationships between fluoride concentration in 45 46 urine of adult and fluoride concentration in drinking water in FNB areas, as well as the period 47 48 of fluoride reducing schemes carried out in FSB areas. 49 50 *: comparing with that in the areas with fluoride concentration was 1.2~2 0 mg/L in 51 52 drinking water. **: comparing with that in the areas with fluoride concentration was 2.0~4.0 53 54 mg/L in drinking water. †: comparing with that of fluoride safe water supply projects built for 55 56 ≤ 5 years. All P values were < 0.001. 57 58 59 24 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 Table 1 Various variables in FNB and FSB areas 4 5 FNB areas FSB areas P-values 6 7 Dental fluorosis ‡ 8 Data collected/Investigated villages (n/N) 1318/1404 558/581 9 10 Subjects (Children) 54855 26931 11 Age (years) 10.07 ± 1.44 10.08 ± 1.44 0.32 12 Female sex (N/%) 25395(46.52) 12610(46.82) 0.42 13 14 Prevalence rate of dental fluorosis (N/%) 27669(50.44) 5121(19.02) < 0.001 # 15 For Dentalpeer fluorosis reviewindex 1.09 only0.40 16 Fluoride content in urine (mg/L) † 17 2.31(1.41, 3.82) 0.90(0.54, 1.51) < 0.001 † 18 Fluoride content in water (mg/L) 2.17(1.66, 2.94) 0.54(0.29, 0.77) < 0.001 19 Skeletal fluorosis 20 ‡ 21 Data collected/Suvey villages (n/N) 1152/1404 470/581 22 Subjects (Adults) 406298 188400 23 Age (years) 42.36 ± 16.79 42.91 ± 16.67 < 0.001 24 25 Female sex (N/%) 196526(48.37) 92711(49.21) < 0.001 26 Prevalent rate of clinical skeletal fluorosis (N/%) 43940(10.81) 9082(4.82) < 0.001 27 Fluoride content in urine (mg/L) † 2.38(1.50, 4.07) 1.05(0.69, 1.75) < 0.001 28 † 29 Fluoride content in water (mg/L) 2.17(1.62, 3.05) 0.53(0.35, 0.75) < 0.001 30 FSB and FNB areas: fluoride safe water supply project had been built and not been built in these 31 32 areas; 33 ‡ Only have dental fluorosis or clinical skeletal fluorosis in some villages; Values are mean ± S.D.
34 for continuous variables; http://bmjopen.bmj.com/ 35 † Log transformed before analysis, and data were expressed as M estimator by Andrew and 36 37 inter quartile range (P25 P75). 38 # The variable was calculated as (questionable number × 0.5 + very mild number ×1 + mild 39 number ×2 + moderate number × 3 + severe number × 4)/the total number of subjects 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 25 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from rate (%) rate Prevalence Prevalence Page 26 of 35
(n) (n) 4309 4309 3.99 9082 4.82 Patients
(n) (n) Subjects
Clinical skeletal fluorosis fluorosis skeletal Clinical 90 29867 17 3064 10.26 3928 96 2.44 59 17858 1000 5.60 (n) (n) 183 107998 121 28749 470 188400 613 2.13 Villages
rate(%) Prevalence
(n) (n) Patients
(n) (n) Dental fluorosis Dental fluorosis Subjects
(n) (n) Villages
areas FSB
17 17 12 785 205 26.11 59 59 59 2231 320 14.34 (n) (n) 187 190 186 182 10948 128 1451 9982 581 119 13.25 2945 558 2985 29.50 26931 200 5121 6.70 19.02 Villages
9.00 18.79 10.81 rate (%)rate Prevalence 26 26
BMJ Open (n) (n)
Patients
http://bmjopen.bmj.com/ (n) (n) Subjects
Clinical skeletal fluorosisskeletal Clinical 15 16 5544 2726 970 293 17.50 10.75 94 20374 2356 11.56 (n) (n) 284 64732 743 12166 312922 28155 1152 1152 406298 43940 Village
Prevalenc (%) ratee on September 23, 2021 by guest. Protected copyright.
(n) (n) Patients
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml (n) (n) Dental fluorosis Dental fluorosis Subjects For peer review only (n) (n) Villages Villages
areas FNB
(n) (n) Villages
6 421 2 337 16 11343 5064 16 44.64 1377 1080 78.43 3 110 108 2938 1137 38.70 (n) (n) Provinces
Jiangsu, Anhui; Southwest:Jiangsu, Sichuan and Yunnan; South: Zhejiang,Hubei, Hunan, Jiangxi, Fujian, Guangxiand Guangdong. Table 2 Prevalence of fluorosis in 5 geographic areas in China in areas geographic 5 in of fluorosis Prevalence 2 Table
All P values in the comparison of dental fluorosis or clinical skeletal fluorosis between FNB and FSB areas were all < 0.001. all0.001. and
Northeast: Northeast: Heilongjiang, Jilin, Northwest: Liaoning; Inner Mongolia, Xinjiang, Qinghai, Ningxia, Gansu, Shaanxi; Central: Beijing, Tianjin, Hebei, Shanxi, Shandong, Henan, province is 26, which is different from the number of 27 provinces in the screening of high fluoride source. fluoride ofsource. screening high the in provinces the number of from 27 isis 26, different which province Total Total 26* 1404 1318 54855 27669 50.44 South 7 19 19 871 319 36.62 Areas Areas Central Central 8 838 838 38326 20069 52.36 Northeast Southwest Northwest 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 27 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 Table 3 Prevalence of fluorosis in different age groups and its prevalent degree in 4 5 FNB and FSB areas. 6 Prevalent rate (N/%) P-values 7 FNB areas FSB areas 8 9 Dental fluorosis 10 Subjects (Children) 54855 26931 11 Age (year) 12 13 8 4499(41.97) 722(13.96) < 0.001 14 9 5050(48.83) 881(16.92) < 0.001 15 For peer10 5613(52.12)review 1001(18.92)only < 0.001 16 11 5579(53.20) 1089(20.55) < 0.001 17 18 12 6929(55.26) 1428(23.03) < 0.001 19 Prevalent degrees 20 Very mild 9862(17.98) 2285(8.48) < 0.001 21 Mild 9959(18.16) 1777(6.60) < 0.001 22 23 Moderate 5999(10.94) 784(2.91) < 0.001 24 Severe 1849(3.37) 275(1.02) < 0.001 25 Clinical skeletal fluorosis 26 27 Subjects (Adults) 406298 188400 28 Age (years) 29 16~25 780(0.96) 77(0.22) < 0.001 30 26~35 2143(3.15) 225(0.71) < 0.001 31 32 36~45 6949(7.43) 1192(2.75) < 0.001 33 46~55 10990(15.93) 2003(5.96) < 0.001
34 56~65 12374(22.83) 2714(10.82) < 0.001 http://bmjopen.bmj.com/ 35 66~ 10704(26.85) 2871(14.89) < 0.001 36 37 Prevalent degrees 38 Mild 26491(6.52) 5236(2.78) < 0.001 39 Moderate 13707(3.37) 3013(1.60) < 0.001 40 3742(0.92) 833(0.44) 41 Severe < 0.001 42 FSB areas: fluoride safe drinking water supply schemes had been built; 43 FNB areas: No fluoride safe drinking water supply scheme is provided. on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 27 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 28 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Locations of 27 provinces in the 5 geographic areas in China 31 76x52mm (300 x 300 DPI) 32 33
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 A: a girl with dental fluorosis; B: an adult with skeletal fluorosis, and photos taken during the investigation. 27 86x48mm (300 x 300 DPI) 28 29 30 31 32 33
34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 30 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 A: Relationships between prevalent rate of dental fluorosis and various fluoride concentrations in the 33 drinking water in FNB areas, and the period of fluoride safe drinking water supply schemes built in FSB areas. B: Relationships between the index of dental fluorosis and urine fluoride concentrations in children,
34 http://bmjopen.bmj.com/ 35 and the fluoride concentration in drinking water in FNB areas, and the period of fluoride safe drinking water supply schemes built in FSB areas. *: comparing with that in the areas with fluoride concentration was 36 1.2~2.0 mg/L in drinking water. **: comparing with that in the areas with fluoride concentration was 37 2.0~4.0 mg/L in drinking water. †: comparing with that of fluoride safe water supply projects built for ≤ 5 38 years. ††: comparing with that of fluoride safe water supply projects built for 5~10 years. All P values were 39 < 0.001. 40 78x58mm (300 x 300 DPI) 41 42
on September 23, 2021 by guest. Protected copyright. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Correlation between fluoride concentrations in drinking-water and variables including A: prevalence of dental fluorosis, B: Dental fluorosis index, C: Fluoride concentration in children urine, D: Prevalence rate of skeletal 32 fluorosis, and E: Fluoride concentrition in adult urine (mg/L). All P values were < 0.001. 33 79x55mm (300 x 300 DPI)
34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 32 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 A: Relationships between prevalent rate of clinical skeletal fluorosis and fluoride concentration in drinking 33 water in FNB areas, as well as the period of fluoride safe water supply schemes built in FSB areas; B: the
34 relationships between fluoride concentration in urine of adult and fluoride concentration in drinking water in http://bmjopen.bmj.com/ 35 FNB areas, as well as the period of fluoride reducing schemes carried out in FSB areas. 36 *: comparing with that in the areas with fluoride concentration was 1.2~2•0 mg/L in drinking water. **: 37 comparing with that in the areas with fluoride concentration was 2.0~4.0 mg/L in drinking water. †: 38 comparing with that of fluoride safe water supply projects built for ≤ 5 years. All P values were < 0.001. 39 79x60mm (300 x 300 DPI) 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from projects projects Subjects covered by by covered Shanxi, , , projects projects Villages 1.2mg/L (n) (n) 1.2mg/L covered by by covered 7 7 7 3406 22 22 43 17393 (n) (n) 327 327 405 329896 1750 1750 4735 3764 6608 1813751 6833883 6841 10827 8998329 Water fluoride concentration >concentration fluorideWater Projects Projects
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Beijing, Tianjin,Beijing, Hebei : projects projects Subjects covered by by covered
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BMJ Open 1.2mg/L (n) (n) 1.2mg/L 80 80 97 96015 62308 4414 4414 3235747 Water fluorideWater http://bmjopen.bmj.com/ 11083 11083 4417891 25194 25194 22491430 40868 30303391 concentration >concentration Villages
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on September 23, 2021 by guest. Protected copyright. subjects
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 87 87 99421 1.2mg/L (n) (n) 1.2mg/L 140 140 79701 4819 4819 3565643 Water fluoride fluoride Water 14847 14847 6231642 31802 29325313 51695 39301720 concentration >concentration Villages Northwest: Northwest: Inner Xinjiang,Mongolia,Qinghai, Ningxia, Gansu, Shaanxi; Central
For peer review only FNB and FSB areas areas and FNB FSB Whole (n) Whole villages villages subjects
6 6 8 60341 3 150726 33719656 7 142896892 727 4411 1190609 4438468 3 3 14970 13278357 27 27 231175 195523982 A nationwide screening of high fluoride ( > 1 > ( fluoride high of screening nationwide A not provided was carried out from 2005 to 2007 in 231 175 villages in 27 provinces all all over China. provinces in 27 175 villages in 231 from 2005 to 2007 out carried was not provided
Supplementary material: Supplementary part of Introduction. in mentioned the were 1 in table The data
Total Total South South Areas Areas Provinces Central Northeast Northwest Northwest Southwest Southwest Table 1 Screening of high fluoride water source and state of fluoride-safe water supply project in 2005-2007 in 2005-2007 water project supply of fluoride-safe state and fluoride source high water Table of Screening 1 Northeast: Heilongjiang,Northeast: Jilin, Liaoning; Shandong, Henan, Southwest:Anhui, Jiangsu; Sichuan, Chongqing and Yunnan; South: Hubei, Zhejiang, Hunan, Jiangxi,and Fujian, Guangxi Guangdong. Page 33 of 35 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Open Page 34 of 35 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies 3 Item 4 No Recommendation 5 Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract 6 7 (b) Provide in the abstract an informative and balanced summary of what was done 8 and what was found 9 Introduction 10 11 Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 12 Objectives 3 State specific objectives, including any prespecified hypotheses 13 Methods 14 15 Study design For4 peer Present key elements review of study design early inonly the paper 16 Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, 17 exposure, follow-up, and data collection 18 Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of 19 participants 20 21 Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect 22 modifiers. Give diagnostic criteria, if applicable 23 Data sources/ 8* For each variable of interest, give sources of data and details of methods of 24 measurement assessment (measurement). Describe comparability of assessment methods if there is 25 26 more than one group 27 Bias 9 Describe any efforts to address potential sources of bias 28 Study size 10 Explain how the study size was arrived at 29 Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, 30 31 describe which groupings were chosen and why 32 Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 33 (b) Describe any methods used to examine subgroups and interactions
34 (c) Explain how missing data were addressed http://bmjopen.bmj.com/ 35 d 36 ( ) If applicable, describe analytical methods taking account of sampling strategy 37 (e) Describe any sensitivity analyses 38 Results 39 40 Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially 41 eligible, examined for eligibility, confirmed eligible, included in the study, 42 completing follow-up, and analysed on September 23, 2021 by guest. Protected copyright. 43 (b) Give reasons for non-participation at each stage 44 (c) Consider use of a flow diagram 45 46 Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and 47 information on exposures and potential confounders 48 (b) Indicate number of participants with missing data for each variable of interest 49 Outcome data 15* Report numbers of outcome events or summary measures 50 51 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and 52 their precision (eg, 95% confidence interval). Make clear which confounders were 53 adjusted for and why they were included 54 (b) Report category boundaries when continuous variables were categorized 55 c 56 ( ) If relevant, consider translating estimates of relative risk into absolute risk for a 57 meaningful time period 58 Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and 59 sensitivity analyses 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml1 Page 35 of 35 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 Discussion 3 Key results 18 Summarise key results with reference to study objectives 4 5 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or 6 imprecision. Discuss both direction and magnitude of any potential bias 7 Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, 8 multiplicity of analyses, results from similar studies, and other relevant evidence 9 10 Generalisability 21 Discuss the generalisability (external validity) of the study results 11 Other information 12 Funding 22 Give the source of funding and the role of the funders for the present study and, if 13 applicable, for the original study on which the present article is based 14 15 For peer review only 16 *Give information separately for exposed and unexposed groups. 17 18 Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and 19 20 published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely 21 available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at 22 http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is 23 available at www.strobe-statement.org. 24
25 26 27 28 29 Dear Editor: 30 31 We tried our best to finish the requirement of Checklist of items in our manuscript “Effects of 32 Fluoride-safe Water Supply on the Prevalence of Fluorosis in China”. 33
34 http://bmjopen.bmj.com/ 35 36 Thanks very much for your attention to our paper. 37 38 39 40 Sincerely yours，，， 41 42
Dian-jun Sun on September 23, 2021 by guest. Protected copyright. 43 44 The Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, 45 Harbin Medical University, Key Lab of Etiologic Epidemiology, Harbin Medical University, 46 Ministry of Health & Education Bureau of Heilongjiang Province; 157 Baojian Road, 47 Nangang District, Harbin Medical University, Harbin, Heilongjiang Province 150081. 48 Telephone: +86 0451 87502695; fax: +86 0451 86676184; e-mail: [email protected]. 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml2 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
A National Cross-sectional Study on Effects of Fluoride-safe Water Supply on the Prevalence of Fluorosis in China
ForJournal: peerBMJ Open review only Manuscript ID: bmjopen-2012-001564.R1
Article Type: Research
Date Submitted by the Author: 28-Jul-2012
Complete List of Authors: Wang, Cheng; Harbin Medical University, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention Gao, Yanhui; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Wang, Wei; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Zhao, Lijun; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Zhang, Wei; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Han, Hepeng; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Shi, Yuxia; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University Yu, Guangqian; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University http://bmjopen.bmj.com/ Sun, Dianjun; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University
Primary Subject Epidemiology Heading:
Secondary Subject Heading: Epidemiology, Public health
Keywords: EPIDEMIOLOGY, PUBLIC HEALTH, FLUOROSIS on September 23, 2021 by guest. Protected copyright.
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1 2 3 4 A National Cross-sectional Study on Effects of Fluoride-safe Water Supply 5 6 on the Prevalence of Fluorosis in China 7 8 Cheng Wang a, Yanhui Gao a, Wei Wang, Lijun Zhao, Wei Zhang, Hepeng Han, Yuxia Shi, 9
10 Guangqian Yu, Dianjun Sun * 11 Design A national cross sectional study in 1985 randomly selected villages in 27 provinces 12 13 (or cities and municipalities) in 5 geographic areas all over China. 14 15 For peer review only 16 All authors are in the Center for Endemic Disease Control, Chinese Center for Disease 17 18 Control and Prevention, Harbin Medical University; Key Lab of Etiologic Epidemiology, 19 20 Harbin Medical University, Education Bureau of Heilongjiang Province & Ministry of Health 21 (23618104), Harbin 150081, China. 22
23 24 a 25 Cheng Wang and Yanhui Gao contributed equally to this work. 26 27 28 Running title: A National Study on Effects of Fluoride safe Water Supply on Fluorosis 29 30 31 Email address of all authors: 32 33 Cheng Wang PhD: [email protected]
34 Yanhui Gao PhD: [email protected] http://bmjopen.bmj.com/ 35 36 Wei Wang BS: [email protected] 37 38 Lijun Zhao PhD: [email protected] 39 Wei Zhang PhD: [email protected] 40 41 Hepeng Han MD: [email protected] 42 43 Yuxia Shi MD: [email protected] on September 23, 2021 by guest. Protected copyright. 44 Guangqian Yu PhD: gq [email protected] 45 46 Dianjun Sun PhD: [email protected] 47 48 49 * Corresponding: Dianjun Sun 50 51 The Center for Endemic Disease Control, Chinese Center for Disease Control and 52 Prevention, Harbin Medical University; Key Lab of Etiologic Epidemiology, Harbin Medical 53 54 University, Ministry of Health & Education Bureau of Heilongjiang Province; 157 Baojian 55 56 Road, Nangang District, Harbin Medical University, Harbin, Heilongjiang Province 150081. 57 Telephone: +86 451 86612695; fax: +86 451 86676184; e mail: [email protected]. 58 59 1 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 Abstract 4 5 Objective To assess the effects of provided fluoride safe drinking water for the prevention 6 7 and control of endemic fluorosis in China. 8 9 Design A national cross sectional study in China. 10 11 Setting In 1985 randomly selected villages in 27 provinces (or cities and municipalities) in 5 12 13 geographic areas all over China. 14 15 ParticipantsFor Involved 81 peer 786 children agedreview from 8 to 12 and 594only 698 adults aged over 16. 16 17 Main outcome measure The prevalence of dental fluorosis and clinical skeletal fluorosis, the 18 fluoride concentrations in the drinking water in study villages and in the urine of subjects. 19 20 Results The study showed that in the villages where the drinking water fluoride concentrations 21 22 were higher than the government standard of 1.2 mg/L, but no fluoride safe drinking water 23 24 supply scheme was provided (FNB areas), the prevalence rate and index of dental fluorosis in 25 26 children, and prevalence rate of clinical skeletal fluorosis in adults were all significantly higher 27 28 than those in the historical endemic fluorosis villages after the fluoride safe drinking water were 29 30 provided (FSB areas). Additionally, the prevalence rate of dental fluorosis as well as clinical 31 32 skeletal fluorosis, and the concentration of fluoride in urine were found increased with the 33 increase of fluoride concentration in drinking water, with significant positive correlations in
34 http://bmjopen.bmj.com/ 35 the FNB areas. While, the prevalence rate of dental fluorosis and clinical skeletal fluorosis in 36 37 different age groups and their degrees of prevalence were significantly lower in the FSB areas 38 39 than those in the FNB areas. 40 41 Conclusions The provision of fluoride safe drinking water supply schemes had significant 42 43 effects on the prevention and control of dental fluorosis and skeletal fluorosis. The study also on September 23, 2021 by guest. Protected copyright. 44 45 indicated that the dental and skeletal fluorosis is still prevailing in the high fluoride drinking 46 47 water areas in China. 48 49 50 Key words: Drinking water; Fluorosis; Dental fluorosis; Clinical skeletal fluorosis 51 52 53 54 55 56 57 58 59 2 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 ARTICLE SUMMARY 4 5 6 Article focus: 7 8 In 2008-2009, through accessing the prevalence of endemic fluorosis in China, the effects of providing 9 10 fluoride-safe drinking water supply on the prevention and control of fluorosis were evaluated. 11 12 Key messages: 13 14 The subjects involved 81,786 children and 594 698 adults in 1985 randomly selected villages in 27 15 For peer review only 16 provinces (or cities and municipalities) in 5 geographic areas all over China. The prevalence rate of dental 17 18 fluorosis as well as clinical skeletal fluorosis, and the concentration of fluoride in urine were found 19 20 increased with the increase of fluoride concentration in drinking water. The provision of fluoride-safe 21 water supply had significant effects on controlling the occurrence and progress of dental fluorosis and 22 23 skeletal fluorosis. Strengths and limitations of this study: 24 25 A national cross-sectional study with large representative samples was carried out on the effects of 26 27 providing fluoride-safe drinking water supply for the prevention and control of endemic fluorosis in China. 28 29 The urine fluoride concentration in adults was tested only in 2009 instead of 2008, which limited the 30 31 acquirement of more information. 32 33
34 http://bmjopen.bmj.com/ 35 36 37 38 Introduction 39 40 41 Fluoride is one of the very few chemicals that have been shown to cause significant health 42 on September 23, 2021 by guest. Protected copyright. 43 effects in people through drinking water. Low fluoride concentration in drinking water (less 44 45 46 than 0.5 ppm) could cause dental caries, lack of formation of dental enamel, and reduced bone 47 48 mineralization.1,2 In contrast, long term consumption of drinking water containing high fluoride 49 50 51 concentration (more than 1 ppm) could cause adverse health effects ranging from mild dental 52 53 fluorosis to crippling skeletal fluorosis depending on the fluoride level and period of 54 55 56 exposure.1,2 Fluorosis induced by exposing to high fluoride in drinking water is quite 57 58 59 3 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 widespread in many countries in the world, including Argentina, Brazil, Canada, China, Eritrea, 5 6 Ethiopia, Germany, India, Indonesia, Israel, Japan, Kenya, Mexico, Niger, Nigeria, Norway, 7 8 9 Pakistan, Saudi Arabia, Senegal, South Africa, Spain, Sri Lanka, Sudan, Thailand, Turkey, 10 11 Uganda, United Republic of Tanzania, and the United States of America.3 It is now becoming a 12 13 4 14 public health problem and an increasing disease burden worldwide, especially for the 15 For peer review only 16 developing countries, such as China. In China, fluorosis from drinking water is a major 17 18 19 endemic disease. A nationwide screening of high fluoride level ( > 1.2mg/L) in drinking water 20 21 in villages where fluoride safe piped drinking water supply had or not provided was carried 22 23 24 out from 2005 to 2007 in 231 175 villages in 27 provinces all over China. In villages where 25 26 fluoride safe piped drinking water supply had been provided, water samples were randomly 27 28 29 taken from the pipelines to test fluoride concentrations in water. In villages where fluoride safe 30 31 piped drinking water supply had not been provided, water samples were randomly collected 32 33 from wells located in the east, west, south, north and center of the villages. This investigation
34 http://bmjopen.bmj.com/ 35 36 found that water fluoride concentration in wells or piped water supplies was higher in 51 695 37 38 39 villages in the 27 provinces than the Chinese national standard of 1.2mg/L, where the 40 41 population is more than 39 million. Most of these villages are located in the geographic areas of 42 43 on September 23, 2021 by guest. Protected copyright. 44 Northeast, Northwest, and Central China. A total 47 057 fluoride safe drinking water supply 45 46 schemes covering 79 190 villages have been surveyed and the fluoride concentration in 14.54 47 48 49 percent of these schemes exceeded the Chinese national standard. Through this investigation, 50 51 the endemic fluorosis areas in these 27 provinces had been identified. 52 53 5 9 54 At present, most of the studies on endemic fluorosis caused by drinking water focused on 55 56 the correlation between fluoride levels in drinking water and urine as well as the prevalence of 57 58 59 4 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 dental fluorosis and skeletal fluorosis. A high correlation between fluorosis prevalence rate and 5 6 the fluoride levels in drinking water has been found. However, with the exception of China,5 8 7 8 9 over the past years, few reports from other countries have reported the provision of 10 11 fluoride safe drinking water supply in the fluoride contaminated areas in large scale. In India, a 12 13 9 14 report in April 2011, mentioned a de fluorination pilot project was carried out at the level of 15 For peer review only 16 community, but unfortunately the project came to a virtual collapse for failing to manage the 17 18 19 project and bear the high cost in the process of maintenance in this project. 20 21 In China, since 1978, the fluoride safe drinking water supply schemes have been built to 22 23 24 provide fluoride safe drinking water to the population in the high fluoride areas and fluorosis 25 26 endemic areas. Through decades’ efforts of the Government, the fluoride concentrations in the 27 28 29 drinking water in many villages have been under control to meet the government standard. On 30 31 the basis of the identified endemic fluorosis areas in these 27 provinces in 2005 to 2007, with 32 33 funds provided by the Government, the present study was carried out in 2008 2009 to access
34 http://bmjopen.bmj.com/ 35 36 the prevalence of endemic fluorosis, and to evaluate the effects of providing fluoride safe 37 38 39 drinking water supply on the prevention and control of fluorosis in China. 40 41 Subjects and Methods 42 43 on September 23, 2021 by guest. Protected copyright. 44 Fluoride-safe water supply schemes 45 46 For the provision of fluoride safe water supply to villages, two technical options were adopted: 47 48 49 (1) using the alternative low fluoride water sources that comply with the national standard (≤ 50 51 1.2 mg/l), and (2) de fluorination through the normal adsorption techniques with activated 52 53 10 54 alumina or electrodialysis method. Two scales of fluoride safe water supply schemes were 55 56 provided: (1) large centralized piped water supply systems that can provide more than 1000 57 58 59 5 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 cubic meter water per day or enough water for more than 10 000 persons daily, and (2) small 5 6 centralized piped water supply schemes that can provide water to the residents below the above 7 8 9 quantity. In the present study, the time of used correctly for the centralized piped water supply 10 11 schemes were investigated, which were as the time of the switch from high fluoride to 12 13 14 fluoride safe water. 15 For peer review only 16 Study areas and contents 17 18 19 In the present study, through accessing the prevalence of endemic fluorosis, the effects of 20 21 providing fluoride safe drinking water supply on the prevention and control of fluorosis were 22 23 24 evaluated. This investigation was carried out in 231 175 selected villages in 27 provinces in 5 25 26 geographic areas all over China (as presented in Figure 1) in 2008 2009. It was based on 27 28 29 outcomes of an early survey which aim was to identify the whole endemic fluorosis areas in 30 31 china in 2005 2007. The aim of early survey is to screening on high fluoride in drinking water 32 33 areas including the previous endemic areas where fluoride safe water supply schemes had been
34 http://bmjopen.bmj.com/ 35 36 build with the current fluoride level in water below 1.2 mg/l. The study villages were divided 37 38 39 into 3 categories for the investigation as follows: (1) villages where water fluoride 40 41 concentration is higher than 1.2mg/Lwith no fluoride safe water supply scheme provided, and 42 43 on September 23, 2021 by guest. Protected copyright. 44 villages in mild endemic fluorosis areas with fluoride safe water supply scheme provided; (2) 45 46 villages where drinking water fluoride concentration is higher than 2.0mg/L with no 47 48 49 fluoride safe water supply scheme provided, and villages in the moderate endemic fluorosis 50 51 areas with fluoride safe water supply scheme provided; and (3) villages where drinking water 52 53 54 fluoride concentration is higher than 4.0mg/L with no fluoride safe water supply scheme 55 56 57 58 59 6 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 7 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 provided, and villages in the severe endemic fluorosis areas with fluoride safe water supply 5 6 schemes provided. 7 8 9 According to the proportion of 4% in every category, 1985 study villages were selected 10 11 randomly for this study with random numbers generated by SPSS (version 13.01S; Beijing 12 13 14 Stats Data Mining Co. Ltd, Beijing, China) in 2008 ~ 2009. In these selected villages, dental 15 For peer review only 16 fluorosis was examined in all children aged from 8 to 12. Besides, 6 children in every age group 17 18 19 from 8 to 12 were randomly selected to test the urine fluoride concentration, and the total 20 21 number of identified children in each village would be 30. If the total numbers of children in 22 23 24 each village are less than 30 or there were less than six children in each age group, all children’s 25 26 urine fluoride concentrations in this village were to be tested. For the test of urine fluoride level 27 28 29 in adults, 20 adults were randomly selected among adult age group over 20 with the ratio male 30 31 to female at 1 to 1. The urine fluoride in adults was tested only in 2009 instead of 2008. The 32 33 prevalence of clinical skeletal fluorosis was investigated in all subjects over 16 years old
34 http://bmjopen.bmj.com/ 35 36 (denoted as adults). The study protocol was approved by the Ethical Committee of the Harbin 37 38 39 Medical University. 40 41 Assessment of fluorosis endemic areas 42 43 on September 23, 2021 by guest. Protected copyright. 44 Endemic fluorosis areas were assessed in the following areas in this study. 45 46 The areas where water fluoride concentration is higher than 1 2 mg/L, are identified as the 47 48 49 endemic fluorosis areas, and divided into three levels according to the prevalence of fluorosis: 50 51 (1) mild endemic fluorosis areas: areas where the prevalence rate of dental fluorosis is 52 53 54 moderate, and the severe patients in the native born residents of 8 to 12 years old children is 55 56 equal to, or less than 20%, or there are mild skeletal fluorosis patients but no moderate skeletal 57 58 59 7 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 8 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 fluorosis patients; (2) moderate endemic fluorosis areas: areas where the prevalence rate of 5 6 dental fluorosis is moderate, and the severe patients in the native born residents of 8 to 12 years 7 8 9 old children is in the range of 20% ~ 40%, or there are skeletal fluorosis patients in moderate 10 11 and severe degrees, but the prevalence of severe skeletal fluorosis is equal to, or less than 2%; 12 13 14 and (3) severe endemic areas: areas where the prevalence rate of dental fluorosis is moderate, 15 For peer review only 16 and the severe patients in the native born residents of 8 to 12 years old children is higher than 17 18 19 40 %, or the prevalence rate of severe skeletal fluorosis is more than 2%. 20 21 Determination of fluoride in drinking water and urine and the diagnosis of dental fluorosis 22 23 24 and skeletal fluorosis 25 26 The water fluoride concentrations in two different areas were tested: (1) in areas where 27 28 29 fluoride safe water supply schemes had been provided (FSB villages); and (2) in areas where 30 31 no fluoride safe water supply scheme is provided (FNB villages). In the FNB villages, 5 water 32 33 samples were randomly collected in the wells located in the east, west, south, north and center
34 http://bmjopen.bmj.com/ 35 36 of each village, that represent the water quality of the whole village. The concentrations of 37 38 39 fluoride in water samples were tested, and the mean value was calculated. In the FSB villages, 40 41 3 water samples from the pipeline of each fluoride safe water supply scheme were randomly 42 43 on September 23, 2021 by guest. Protected copyright. 44 collected and the fluoride concentrations were tested, and the mean value was calculated. The 45 46 urina sanguinis of the study subjects were collected in the morning for testing. The 47 48 49 concentrations of fluoride in drinking water samples and urine samples are analyzed with ion 50 51 selective electrode methods (WS/T106 1999 11 for water and WS/T89 1996 12 for urine). 52 53 13 54 Dental fluorosis was diagnosed using Dean’s method recommended by WHO. An 55 56 individual’s fluorosis condition is based on the most severe form of fluorosis found on two or 57 58 59 8 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 9 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 more teeth. An individual’s dental status can be classified into six parts: normal, questionable, 5 6 very mild, mild, moderate and severe. The clinical diagnosis of skeletal fluorosis followed the 7 8 14 9 Diagnostic Criteria of Endemic Skeletal Fluorosis (WS 192 2008) . An individual’s skeletal 10 11 fluorosis status is based on the severe form of persistent rest pain of Neck, waist and the large 12 13 14 joints of limb, severe dyskinesia, limb deformity, and even paralysis, and can be classified into 15 For peer review only 16 three parts: mild, moderate and severe. 17 18 19 Quality Control of project implementation 20 21 This study was carried out by the Centre for Endemic Disease Control, Chinese Centre for 22 23 24 Disease Control and Prevention led by the Ministry of Health. The study was planned through 25 26 discussion with experts in the fields of Chinese endemic and epidemic diseases, and the Quality 27 28 29 Control of project implementation was carried out in several aspects including: (1) according to 30 31 the requirements in the Government guidelines on "the project management scheme" and "the 32 33 project technical solutions" of national drinking water fluorosis survey, all provinces,
34 http://bmjopen.bmj.com/ 35 36 autonomous regions and municipalities were requested to develop their own respective 37 38 39 implementation plans in accordance with the local conditions, and to carry out this study; (2) 40 41 the provincial institutions for disease prevention and control selected survey villages in 42 43 on September 23, 2021 by guest. Protected copyright. 44 accordance with the principles of randomization, and then sent the survey plan to the concerned 45 46 counties where the selected villages belonged. The institutions for disease prevention and 47 48 49 control in the respective concerned counties were then responsible for the survey in the selected 50 51 villages; (3) the concerned technicians for the analysis of fluoride concentrations in water and 52 53 54 urine, diagnosis of dental fluorosis and clinical skeletal fluorosis, and data entry were all trained 55 56 in provincial institutions, and the concerned staff at provincial levels were trained by the 57 58 59 9 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 10 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 national experts in the national center of endemic disease to ensure that uniform methods and 5 6 standard techniques were applied in the investigation to keep the accuracy of illness diagnosis 7 8 9 and feedback in time; (4) the provincial institutions were responsible for quality 10 11 control/assessment on the analysis of fluoride concentrations in water and urine samples in all 12 13 14 concerned county level laboratories, and the external quality control samples were from the 15 For peer review only 16 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention. The 17 18 19 laboratories taking up the test of fluoride concentrations in water and urine samples were 20 21 permitted to carry out the analysis tasks arranged by provincial agencies if they passed the 22 23 24 assessment by external quality control; (5) after the provincial institutions completed the first 25 26 supervision and inspection on assessment conducted in project villages, and if some problems 27 28 29 were found/detected, corrections should be made in due course for further project 30 31 implementation. At the end of the project, the consistency of project implementation, the 32 33 rationality of sample collections and sampling methods, as well as the accuracy of the analysis
34 http://bmjopen.bmj.com/ 35 36 technologies and disease diagnostic were all needed to be assessed. 37 38 39 Statistical analysis 40 41 Statistical analysis was carried out in all FSB and FNB villages respectively. In FSB areas, the 42 43 on September 23, 2021 by guest. Protected copyright. 44 prevalence of fluorosis was compared in three stages, based on the length of time when the 45 46 fluoride safe water supply schemes were provided, equal to or less than 5 years, between 5 47 48 49 to10 years and more than 10 years. In FNB areas (the FSB villages where fluoride 50 51 concentration in water supply schemes is higher than 1.2 mg/L were considered as fluoride safe 52 53 54 water supply non provided areas), the prevalence of fluorosis was compared according to the 55 56 fluoride concentrations in drinking water, i.e. between 1.2~2.0mg/l, 2.0~4.0 mg/l, and higher 57 58 59 10 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 11 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 than 4.0 mg/l. Statistical analysis was carried out using SPSS. Data were presented as mean ± 5 6 standard deviation (SD) or M estimators by Andrew with inter quartile range as appropriate. 7 8 9 Data that were not normally distributed, as determined with the Kolmogorov Smirnov test, 10 11 were logarithmically transformed to obtain near normality before analysis. Chi square test was 12 13 14 used to compare categorical variables. Bivariate Correlations with spearman was used to 15 For peer review only 16 analyze the correlation between variables. All P values are 2 tailed and P value < 0.05 was 17 18 19 considered as significant for all statistical analyses in this study. 20 21 22 23 24 Results 25 26 In the FSB and FNB areas, 1404 and 581 villages were selected, respectively. A total of 676 27 28 29 484 study subjects were investigated including 81 786 children and 594 698 adults. The 30 31 prevalence of dental fluorosis was investigated in 1876 villages covering 1318 FNB villages 32 33 and 558 FSB villages. The prevalence of clinical skeletal fluorosis was investigated in 1622
34 http://bmjopen.bmj.com/ 35 36 villages consisting of 1152 FNB villages and 470 FSB villages respectively (In some villages, 37 38 39 only dental fluorosis and/or clinical skeletal fluorosis were surveyed) as presented in Table 1 40 41 and 2. 42 43 on September 23, 2021 by guest. Protected copyright. 44 The prevalence of dental fluorosis and clinical skeletal fluorosis was compared between FSB 45 46 and FNB areas. The photographs taken in the surveyed villages represented the patients 47 48 49 suffering from dental fluorosis and skeletal fluorosis (Figure 2). 50 51 Prevalence of dental and skeletal fluorosis in five geographic areas of China 52 53 54 55 56 57 58 59 11 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 12 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Prevalence rates of dental fluorosis and clinical skeletal fluorosis in FNB areas were 5 6 significantly higher than that in FSB areas in 5 geographic parts in China as presented in Table 7 8 9 111. 10 11 Comparison of the prevalence of dental fluorosis, skeletal fluorosis, fluoride concentrations 12 13 14 in drinking water and urine between the FNB and FSB areas 15 For peer review only 16 Children aged 8 to 12 including 54 855 in FNB areas and 26 931 in FSB villages were 17 18 19 investigated for the prevalence of dental fluorosis, and adults aged more than 16 including 20 21 406 298 in FNB areas and 188 400 in FSB villages were investigated for the prevalence of 22 23 24 skeletal fluorosis. The prevalence rates of dental fluorosis and clinical skeletal fluorosis, 25 26 dental fluorosis index, and fluoride concentration in urine and in drinking water were 27 28 29 significant lower in FSB areas compared to that in FNB areas (Table 2). Prevalence rates of 30 31 dental fluorosis and clinical skeletal fluorosis in different ages and their prevalent degrees 32 33 were all significantly lower in FSB areas than FNB areas (Table 3).
34 http://bmjopen.bmj.com/ 35 36 Relationships between the prevalence rate of dental fluorosis, dental fluorosis index, 37 38 39 fluoride concentrations in urine and in drinking-water in FNB areas, and the period of the 40 41 fluoride-safe water supply provided in FSB areas 42 43 on September 23, 2021 by guest. Protected copyright. 44 The prevalence rate of dental fluorosis increased significantly with the increase of water 45 46 fluoride concentration in FNB areas. The prevalence rates of dental fluorosis were 40.82%, 47 48 49 55.06% and 67.20% in these areas where fluoride concentration in drinking water was 50 51 1.2~2.0mg/l, 2.0~4.0 mg/l and > 4.0mg/l respectively as shown in Figure 3, A. Significant 52 53 54 positive correlation between the prevalence rate of dental fluorosis and fluoride concentrations 55 56 in drinking water (R = 0.33, P < 0.001) is presented in Figure 4, A. The prevalence rate of 57 58 59 12 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 13 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 dental fluorosis decreased with the increase of time of the availability of fluoride safe water in 5 6 the FSB areas. The prevalence rates of dental fluorosis were 24.54%, 21.35% and 13.9%, 7 8 9 respectively, in the FSB villages where fluoride safe water supply schemes were provided for 10 11 equal to or less than 5 years, between 5~10 years and more than 10 years. And the prevalence 12 13 14 rate of dental fluorosis in the FSB areas where the availability of fluoride safe water supply less 15 For peer review only 16 than 5 years (24.54%) was lower than that in the areas where fluoride concentration between 17 18 19 1.2~2.0 mg/l in FNB areas (the prevalence rate of dental fluorosis is lower than 30 percent, 20 21 which is the standard could be thought as un prevalence for the dental fluorosis in China) as 22 23 24 shown in Figure 3. A. 25 26 The dental fluorosis index and fluoride concentration in urine increased significantly with the 27 28 29 increase of fluoride concentration in drinking water in the FNB areas. The dental fluorosis 30 31 indices were 0.86, 1.17 and 1.53 and fluoride concentration in urine were 1.97 (1.21, 3.00), 32 33 2.53(1.50, 4.02), 3.41(2.12, 5.29) respectively in these FNB areas where ranges of fluoride
34 http://bmjopen.bmj.com/ 35 36 concentration in drinking water were 1.2~2.0mg/L, 2.0~4.0 mg/L, and > 4 0mg/L. And there 37 38 39 was a significant positive correlation between dental fluorosis index (R = 0.34, P < 0.001), 40 41 urine fluoride concentration (R = 0.43, P < 0.001) in children and fluoride concentration in 42 43 on September 23, 2021 by guest. Protected copyright. 44 drinking water as presented in Figure 4, B and C. In the FSB areas, the fluoride concentration 45 46 in urine was significantly lower in villages where fluoride safe drinking water supply had been 47 48 49 provided for more than 5 years compared to that of less than 5 years. The fluoride concentration 50 51 in urine were 1.00(0.61, 1.89), 0.83(0.5, 1.36) and 0.85(0.52, 1.33) respectively in areas where 52 53 54 fluoride safe water supply schemes had been provided for equal to or less than 5 years, between 55 56 5 to 10 years and more than 10 years. And the levels of urinary fluoride and dental fluorosis 57 58 59 13 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 14 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 index [1.00(0.61, 1.89) and 0.53] in the FSB areas where the availability of fluoride safe water 5 6 supply equal to or less than 5 years were lower than that in the areas where fluoride 7 8 9 concentration between 1.2~2.0 mg/l in FNB areas as illustrating in Figure 3. B. 10 11 Relationships between the prevalence rate of clinical skeletal fluorosis, fluoride 12 13 14 concentrations in urine and in drinking-water in FNB areas and the length of time of 15 For peer review only 16 fluoride-safe drinking water provision in FSB areas 17 18 19 The prevalence rate of clinical skeletal fluorosis increased significantly with the increase of 20 21 fluoride concentration in drinking water in the FNB areas. As presented in Figure 5, A, the 22 23 24 prevalence rate of clinical skeletal fluorosis increased (7.28%, 11.54% and 22.64%) with the 25 26 increase of fluoride concentrations in drinking water (1.2~2.0mg/l, 2.0~4.0 mg/l, and > 4.0mg/l) 27 28 29 respectively. And there was a significant positive correlation between the prevalence rate of 30 31 clinical skeletal fluorosis and fluoride concentration in drinking water (R = 0.20, P < 0.001) as 32 33 illustrated in Figure 4, D. In the FSB areas, the prevalence rate of clinical skeletal fluorosis
34 http://bmjopen.bmj.com/ 35 36 increased slightly and then subsequently decreased as the period of providing the fluoride safe 37 38 39 drinking water supply continuing to more than 10 years, but still its value was lower than that in 40 41 the FNB areas where the drinking water fluoride concentration between 1.2~2.0 mg/l as shown 42 43 on September 23, 2021 by guest. Protected copyright. 44 in Figure 5. A. 45 46 The fluoride concentrations in urine were found increased significantly with the increase of 47 48 49 fluoride concentrations in drinking water. Fluoride concentrations in urine were 1.99(1.30, 50 51 3.20), 2.97(1.73, 4.83), 3.77(2.17, 6.79) in areas where fluoride concentrations in drinking 52 53 54 water were 1.2~2.0mg/l, 2.0~4.0 mg/l, and > 4.0mg/l, respectively as illustrated in Figure 5. A. 55 56 Positive correlation between urine fluoride concentrations in adults and fluoride concentration 57 58 59 14 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 15 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 in drinking water (R = 0.42, P < 0.001) is presented in Figure 4. E. Urine fluoride 5 6 concentrations remains unchanged in FSB areas in longer period of available fluoride safe 7 8 9 drinking water supply, but it is lower than those in the FNB areas where drinking water fluoride 10 11 concentration is between 1.2 2.0 mg/l as shown in Figure 5. B. 12 13 14 Discussion 15 For peer review only 16 Our study showed that provision of fluoride safe drinking water supply within the 17 18 19 government standard of 1.2 mg/l have significant effects on the control of dental fluorosis and 20 21 skeletal fluorosis, and decreasing fluoride concentrations in urine in the areas with high 22 23 24 fluoride in drinking water. Besides, this study also provided a scientific foundation for 25 26 assessing the prevalence of fluorosis in drinking water. The present study also indicated that 27 28 29 the prevalence rates of dental fluorosis in children aged 8 ~ 12 and skeletal fluorosis in adults 30 31 were 50.44 percent and 10.81 percent respectively in FNB areas (the FNB areas covered the 32 33 villages in the provinces where no fluoride safe drinking water supply is provided, and the
34 http://bmjopen.bmj.com/ 35 36 villages where fluoride safe drinking water supply schemes were provided with the water 37 38 39 fluoride concentrations in drinking water exceeding the government standard). Based on the 40 41 outcomes of this study, it is estimated that 1.35 million of children aged from 8 to 12 having 42 43 on September 23, 2021 by guest. Protected copyright. 44 dental fluorosis and 3.15 million adults in the age groups of more than 16 years suffering from 45 46 both dental fluorosis and skeletal fluorosis in FNB areas and in some FSB areas where the 47 48 49 fluoride level in drinking water exceeded the government standard. These fluorosis patients 50 51 were mainly distributed in the northeast, northwest and central geographic parts in China. 52 53 54 Moreover, in these geographic areas, the endemic fluorosis is relatively more severe in the 55 56 provinces of Heilongjiang, Inner Mongolia, Xinjiang, Gansu, Tianjin, Hebei, Henan, Jiangsu, 57 58 59 15 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Shandong, and Anhui than in other provinces. These provinces would be the priority areas 5 6 when the fluoride safe water supply schemes are provided in the future. 7 8 9 The relationships between levels of drinking water fluoride and urine fluoride, dental 10 11 fluorosis and skeletal fluorosis have been reported in studies 15 19 in Japan, Indian, Germany 12 13 14 and South Africa. The results in the FNB areas in the present study were consistent with these 15 For peer review only 16 former investigations that there were significantly higher prevalence rates of dental fluorosis 17 18 15 18 19, 20 21 19 , skeletal fluorosis and higher urine fluoride concentrations in areas with high 20 21 fluoride concentrations in drinking water, Excessive intake of fluoride can cause the dental 22 23 24 fluorosis and skeletal fluorosis, even with severe dyskinesia, limb deformity and even 25 26 paralysis.14, 22, 23, 24 Fluoride can also damage the digestive, nervous, immune, and urinary 27
28 25 26, 27 29 systems. Moreover, the fluoride can also damage the intelligence of children. Therefore, 30 31 disruption or damage of these systems can have a wide range of effects on the body. 32 33 Based on the severe harmful effects of fluorosis on human beings, some measures should be
34 http://bmjopen.bmj.com/ 35 36 taken to control the occurrence and progress of fluorosis. First, the effects of pharmaceutical 37 38 28 39 intervention on dental fluorosis and skeletal fluorosis could not let us feel satisfied enough, 40 41 and severe patients finally need to carry out surgery, which result was also indeterminate; 42 43 on September 23, 2021 by guest. Protected copyright. 44 second, because the bioavailability of fluoride is generally reduced in humans when consumed 45 46 milk (decreased to 70%)29 or a calcium (decreased to 60%) rich diet, 30 it has been highly 47 48 49 recommended that the inhabitants of fluoride contaminated areas should incorporate 50 51 calcium rich foods in their routine diet. But such measures could not fundamentally solve such 52 53 54 a problem, and it could be hard to implement in poverty areas. Therefore, changing the 55 56 drinking water sources used for the inhabitants living in fluoride contaminated areas would be 57 58 59 16 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 an appropriate and reasonable way for prevention and control of the fluorosis. In 1995, a study 5 6 by Boyle et al 19 in Gasp region, Quebec of Canada mentioned the well drilling should be in 7 8 9 different deeps according to the F levels in different groundwater layers through studying the 10 11 relationships between the prevalence of fluorosis and F levels in groundwater in different areas. 12 13 14 And Boyle indicated that Hydrogeochemists, hydrologists, health officials, and environmental 15 For peer review only 16 regulators should work closely together in order to efficiently eradicate the risk of skeletal 17 18 19 fluorosis from drinking water associated with geological environments where such risks exist. 20 21 Although some advices were proposed, with the exception of China, 5 8 there were few relative 22 23 24 reports in others countries on providing large scale fluoride safe water in the past many years. 25 26 These studies 5 8 in China reported the fluoride concentration in drinking water and urine, and 27 28 29 the prevalence rate of dental fluorosis or skeletal fluorosis after the fluoride safe drinking 30 31 water supply schemes have been provided. However, most of the studies we mentioned above 32 33 were carried out in one or several provinces not in the national scale, and the selected villages
34 http://bmjopen.bmj.com/ 35 36 were seldom than the present study. In addition, these studies only reported several values of 37 38 39 the fluoride concentration in drinking water and/or urine, and/or the prevalence rate of dental 40 41 fluorosis and/or skeletal fluorosis, not including all of them. Furthermore, these above values 42 43 on September 23, 2021 by guest. Protected copyright. 44 were not compared between FNB and FSB areas, and the effects of fluoride safe water supply 45 46 on the prevalence of fluorosis had not been evaluated. 47 48 49 In China, the fluoride safe drinking water supply schemes have been provided in high water 50 51 fluoride areas for many years. Through years of cooperation between various agencies, such as 52 53 54 water resources, geology and health, rich experience has been accumulated as basis on the 55 56 implementation of this study. However, some issues were observed during the study period, 57 58 59 17 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 such as problems of difficulty in locating low fluoride level of drinking water sources and/or 5 6 proper lining of wells after those wells have been drilled and proper maintenance, supervision 7 8 9 and operation of the fluoride safe drinking water supply schemes. In addition, some of the 10 11 fluoride safe drinking water supply schemes were found to have fluoride concentration more 12 13 14 than 1.2 mg/l. In fact, these ‘fluoride safe’ drinking water supply schemes were no longer 15 For peer review only 16 ‘fluoride safe’ at all. In fact, these water schemes were providing ‘non fluoride safe’ drinking 17 18 19 water, which is harmful to the residents’ health by inducing dental fluorosis and skeletal 20 21 fluorosis. The fact was that before the fluoride safe water supply schemes were provided, the 22 23 24 local residents were drinking water from their own tube wells with various depths, and not all 25 26 tube wells had high fluoride concentration (based on the geological formation). Therefore, it is 27 28 29 extremely important to monitor the fluoride level in all fluoride safe drinking water supply 30 31 schemes by starting from identifying the water sources to operation and maintenance, and 32 33 ensure that the fluoride level in these fluoride safe water schemes meets the government
34 http://bmjopen.bmj.com/ 35 36 standards, and to carry out the surveillance of the prevalence of fluorosis for cross checking of 37 38 39 the fluoride concentrations in the fluoride safe drinking water supply schemes for long term 40 41 sustainability of supplying the fluoride safe drinking water in FSB areas for the prevention and 42 43 on September 23, 2021 by guest. Protected copyright. 44 control of endemic fluorosis. 45 46 Conclusions 47 48 In summary, the fluoride safe drinking water supply schemes had been provided in various 49 50 localities in provinces in China for decades. The study found that providing fluoride safe water 51 52 53 supply had significant effects on controlling the occurrence and progress of dental fluorosis and 54 55 skeletal fluorosis. The study also indicates that the dental and skeletal fluorosis is still 56 57 58 prevailing in the high fluoride drinking water areas in China. To control and prevent the 59 18 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 continuous spreading of endemic fluorosis, we suggest that government’s effort be given to 5 6 provide the fluoride safe drinking water supply schemes with proper operation and 7 8 9 maintenance in all high fluoride drinking water areas in China. 10 11 Acknowledgements 12 13 14 We are grateful to the generous support by many researchers and medical professionals from 15 For peer review only 16 the various Centers for Endemic Disease Control in the 27 provinces, autonomous regions and 17 18 19 municipalities and for their continuous efforts and collaboration during this study. We wish to 20 21 acknowledge the close cooperation of many fluorosis patients who allowed us to do the 22 23 24 examination and checking up for this study. 25 26 Contributors 27 28 29 DJ Sun contributed to the conception and design of the study. C Wang and YH Gao 30 31 contributed to the analysis of data. C Wang, YH Gao, W Wang, LJ Zhao, W Zhang, HP Han, 32 33 YX Shi, GQ Yu, DJ Sun have contributed to the acquisition and interpretation of data,
34 http://bmjopen.bmj.com/ 35 36 drafting the article and revisions for important intellectual content and final approval of the 37 38 39 version to be published. 40 41 Funding: This work was supported by the Chinese government for Endemic Disease Control 42 43 on September 23, 2021 by guest. Protected copyright. 44 in 2008 ~ 2009 years. 45 46 Conflicts of interest 47 48 49 We declare that we have no conflicts of interest. 50 51 Ethics approval 52 53 54 Ethical approval was provided by the Ethical Committee at the Harbin Medical University. 55 56 57 58 59 19 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Data Sharing Statement 5 6 There is no additional data available. 7 8 9 10 11 Exclusive licence 12 13 The Corresponding Author has the right to grant on behalf of all authors and does grant on 14 15 behalf of all Forauthors, an exclusivepeer licence review (or non exclusive for onlygovernment employees) on a 16 worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if 17 18 accepted) to be published in BMJ editions and any other BMJPGL products and sublicences 19 20 to exploit all subsidiary rights, as set out in our licence. 21 22 23 24 25 26 27 28 29 30 31 32 33
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1 2 3 4 26 Ding YP, Gao YH, Sun HX, et al. The relationships between low levels of urine fluoride 5 6 on children’s intelligence,dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner 7 8 9 Mongolia, China. J. Hazard. Mater 2011; 186: 1942 1946. 10 11 27 Wang SX, Wang ZH, Cheng XT, et al. Arsenic and fluoride exposure in drinking water: 12 13 14 children's IQ and growth in Shanyin county, Shanxi province, China. Environ Health 15 For peer review only 16 Persp 2007; 115: 643 647. 17 18 19 28 Sang ZC, Zhou W, Zhang ZJ, et al. X ray analysis on 114 patients with moderate 20 21 endemic skeletal fluorosis by treatment of Guo's Chinese herbal. Zhongguo Gu Shang 22 23 24 2010; 23: 379 382. [Article in Chinese] 25 26 29 Ekstrand J, Ehrnebo M. Influence of milk products on fluoride bioavailability in man. 27 28 29 Eur J Clin Pharmacol 1979; 16: 211–215. 30 31 30 Shulman ER, Vallejo M. Effect of gastric contents on the bioavailability of fluoride in 32 33 humans. Pediatr Dent 1990; 12:237–240
34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 on September 23, 2021 by guest. Protected copyright. 43 44 45 46 47 48 49 50 51 52 53 54 55
56 57 58 59 24 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 25 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from
1 2 3 4 Figure legends 5 6 Figure 1. Locations of 27 provinces in the 5 geographic areas in China. 7 8 Figure 2. A: a girl with dental fluorosis; B: an adult with skeletal fluorosis, and photos taken 9 10 during the investigation. 11 12 Figure 3. A: Relationships between prevalence rate of dental fluorosis and various fluoride 13 14 concentrations in the drinking water in FNB areas, and the period of fluoride safe drinking 15 For peer review only 16 water supply schemes built in FSB areas. B: Relationships between the index of dental 17 18 fluorosis and urine fluoride concentrations in children, and the fluoride concentration in 19 20 drinking water in FNB areas, and the period of fluoride safe drinking water supply schemes 21 22 built in FSB areas. *: comparing with that in the areas with fluoride concentration was 23 24 1.2~2.0 mg/L in drinking water. **: comparing with that in the areas with fluoride 25 26 concentration was 2.0~4.0 mg/L in drinking water. †: comparing with that of fluoride safe 27 28 water supply projects built for ≤ 5 years. ††: comparing with that of fluoride safe water 29 30 supply projects built for 5~10 years. All P values were < 0.001. 31 32 Figure 4 Correlation between fluoride concentrations in drinking water and variables 33 including A: prevalence of dental fluorosis, B: Dental fluorosis index, C: Fluoride 34 http://bmjopen.bmj.com/ 35 36 concentration in children urine, D: Prevalence rate of skeletal fluorosis, and E: Fluoride 37 38 concentrition in adult urine (mg/L). All P values were < 0.001. 39 40 Figure 5 A: Relationships between prevalence rate of clinical skeletal fluorosis and fluoride 41 42 concentration in drinking water in FNB areas, as well as the period of fluoride safe water 43 on September 23, 2021 by guest. Protected copyright. 44 supply schemes built in FSB areas; B: the relationships between fluoride concentration in 45 46 urine of adult and fluoride concentration in drinking water in FNB areas, as well as the period 47 48 of fluoride reducing schemes carried out in FSB areas. 49 50 *: comparing with that in the areas with fluoride concentration was 1.2~2 0 mg/L in 51 52 drinking water. **: comparing with that in the areas with fluoride concentration was 2.0~4.0 53 54 mg/L in drinking water. †: comparing with that of fluoride safe water supply projects built for 55 56 ≤ 5 years. All P values were < 0.001. 57 58 59 25 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from rate (%) rate Prevalence Prevalence Page 26 of 36
(n) (n) 4309 4309 3.99 9082 4.82 Patients
(n) (n) Subjects
Clinical skeletal fluorosis fluorosis skeletal Clinical 90 29867 17 3064 10.26 3928 96 2.44 59 17858 1000 5.60 (n) (n) 183 107998 121 28749 470 188400 613 2.13 Villages
rate(%) Prevalence
(n) (n) Patients
(n) (n) Dental fluorosis Dental fluorosis Subjects
(n) (n) Villages
areas FSB
17 17 12 785 205 26.11 59 59 59 2231 320 14.34 (n) (n) 187 190 186 182 10948 128 1451 9982 581 119 13.25 2945 558 2985 29.50 26931 200 5121 6.70 19.02 Villages
9.00 18.79 10.81 rate (%)rate Prevalence 26 26
BMJ Open (n) (n)
Patients
http://bmjopen.bmj.com/ (n) (n) Subjects
Clinical skeletal fluorosisskeletal Clinical 15 16 5544 2726 970 293 17.50 10.75 94 20374 2356 11.56 (n) (n) 284 64732 743 12166 312922 28155 1152 1152 406298 43940 Village
Prevalenc (%) ratee on September 23, 2021 by guest. Protected copyright.
(n) (n) Patients
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml (n) (n) Dental fluorosis Dental fluorosis Subjects For peer review only (n) (n) Villages Villages
areas FNB
(n) (n) Villages
6 421 2 337 16 11343 5064 16 44.64 1377 1080 78.43 3 110 108 2938 1137 38.70 (n) (n) Provinces
Jiangsu, Anhui; Southwest:Jiangsu, Sichuan and Yunnan; South: Zhejiang,Hubei, Hunan, Jiangxi, Fujian, Guangxiand Guangdong. Table 1 Prevalence of fluorosis in 5 geographic areas in China in areas geographic 5 in of fluorosis Prevalence 1 Table
All P values in the comparison of dental fluorosis or clinical skeletal fluorosis between FNB and FSB areas were all < 0.001. all0.001. and Northeast: Northeast: Heilongjiang, Jilin, Northwest: Liaoning; Inner Mongolia, Xinjiang, Qinghai, Ningxia, Gansu, Shaanxi; Central: Beijing, Tianjin, Hebei, Shanxi, Shandong, Henan, province is 26, which is different from the number of 27 provinces in the screening of high fluoride source. fluoride ofsource. screening high the in provinces the number of from 27 isis 26, different which province Total Total 26* 1404 1318 54855 27669 50.44 South 7 19 19 871 319 36.62 Areas Areas Central Central 8 838 838 38326 20069 52.36 Northeast Southwest Northwest 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 27 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 Table 2 Various variables in FNB and FSB areas 4 5 FNB areas FSB areas P-values 6 7 Dental fluorosis 8 Data collected/Investigated villages (n/N)‡ 9 1318/1404 558/581 10 Subjects (Children) 54855 26931 11 Age (years) 10.07 ± 1.44 10.08 ± 1.44 0.32 12 Female sex (N/%) 25395(46.52) 12610(46.82) 0.42 13 14 Prevalence rate of dental fluorosis (N/%) 27669(50.44) 5121(19.02) < 0.001 # 15 For Dentalpeer fluorosis reviewindex 1.09 only0.40 16 Fluoride content in urine (mg/L) † 17 2.31(1.41, 3.82) 0.90(0.54, 1.51) < 0.001 † 18 Fluoride content in water (mg/L) 2.17(1.66, 2.94) 0.54(0.29, 0.77) < 0.001 19 Skeletal fluorosis 20 ‡ 21 Data collected/Suvey villages (n/N) 1152/1404 470/581 22 Subjects (Adults) 406298 188400 23 Age (years) 42.36 ± 16.79 42.91 ± 16.67 < 0.001 24 25 Female sex (N/%) 196526(48.37) 92711(49.21) < 0.001 26 Prevalence rate of clinical skeletal fluorosis (N/%) 43940(10.81) 9082(4.82) < 0.001 27 † 28 Fluoride content in urine (mg/L) 2.38(1.50, 4.07) 1.05(0.69, 1.75) < 0.001 † 29 Fluoride content in water (mg/L) 2.17(1.62, 3.05) 0.53(0.35, 0.75) < 0.001 30 FSB and FNB areas: fluoride safe water supply project had been built and not been built in these 31 areas; 32 ‡ Only have dental fluorosis or clinical skeletal fluorosis in some villages; Values are mean ± S.D. 33 for continuous variables; 34 http://bmjopen.bmj.com/ 35 † Log transformed before analysis, and data were expressed as M estimator by Andrew and 36 inter quartile range (P25 P75). 37 # The variable was calculated as (questionable number × 0.5 + very mild number ×1 + mild 38 39 number ×2 + moderate number × 3 + severe number × 4)/the total number of subjects 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 27 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 28 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 Table 3 Prevalence of fluorosis in different age groups and its prevalent degree in 4 5 FNB and FSB areas. 6 Prevalence rate (N/%) P-values 7 FNB areas FSB areas 8 9 Dental fluorosis 10 Subjects (Children) 54855 26931 11 Age (year) 12 13 8 4499(41.97) 722(13.96) < 0.001 14 9 5050(48.83) 881(16.92) < 0.001 15 For peer10 5613(52.12)review 1001(18.92)only < 0.001 16 11 5579(53.20) 1089(20.55) < 0.001 17 18 12 6929(55.26) 1428(23.03) < 0.001 19 Prevalent degrees 20 Very mild 9862(17.98) 2285(8.48) < 0.001 21 Mild 9959(18.16) 1777(6.60) < 0.001 22 23 Moderate 5999(10.94) 784(2.91) < 0.001 24 Severe 1849(3.37) 275(1.02) < 0.001 25 Clinical skeletal fluorosis 26 27 Subjects (Adults) 406298 188400 28 Age (years) 29 16~25 780(0.96) 77(0.22) < 0.001 30 26~35 2143(3.15) 225(0.71) < 0.001 31 32 36~45 6949(7.43) 1192(2.75) < 0.001 33 46~55 10990(15.93) 2003(5.96) < 0.001 34 56~65 12374(22.83) 2714(10.82) < 0.001 http://bmjopen.bmj.com/ 35 66~ 10704(26.85) 2871(14.89) < 0.001 36 37 Prevalent degrees 38 Mild 26491(6.52) 5236(2.78) < 0.001 39 Moderate 13707(3.37) 3013(1.60) < 0.001 40 3742(0.92) 833(0.44) 41 Severe < 0.001 42 FSB areas: fluoride safe drinking water supply schemes had been built; 43 FNB areas: No fluoride safe drinking water supply scheme is provided. on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 28 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 29 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Locations of 27 provinces in the 5 geographic areas in China. 31 76x52mm (300 x 300 DPI) 32 33 34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 30 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 A: a girl with dental fluorosis; B: an adult with skeletal fluorosis, and photos taken during the investigation. 27 86x48mm (300 x 300 DPI) 28 29 30 31 32 33 34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 31 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 A: Relationships between prevalence rate of dental fluorosis and various fluoride concentrations in the 33 drinking water in FNB areas, and the period of fluoride safe drinking water supply schemes built in FSB areas. B: Relationships between the index of dental fluorosis and urine fluoride concentrations in children, 34 http://bmjopen.bmj.com/ 35 and the fluoride concentration in drinking water in FNB areas, and the period of fluoride safe drinking water supply schemes built in FSB areas. *: comparing with that in the areas with fluoride concentration was 36 1.2~2.0 mg/L in drinking water. **: comparing with that in the areas with fluoride concentration was 37 2.0~4.0 mg/L in drinking water. †: comparing with that of fluoride safe water supply projects built for ≤ 5 38 years. ††: comparing with that of fluoride safe water supply projects built for 5~10 years. All P values were 39 < 0.001. 40 78x58mm (300 x 300 DPI) 41 42 on September 23, 2021 by guest. Protected copyright. 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 32 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Correlation between fluoride concentrations in drinking-water and variables including A: prevalence of dental fluorosis, B: Dental fluorosis index, C: Fluoride concentration in children urine, D: Prevalence rate of skeletal 32 fluorosis, and E: Fluoride concentrition in adult urine (mg/L). All P values were < 0.001. 33 79x55mm (300 x 300 DPI) 34 http://bmjopen.bmj.com/ 35 36 37 38 39 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 33 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 A: Relationships between prevalence rate of clinical skeletal fluorosis and fluoride concentration in drinking- 33 water in FNB areas, as well as the period of fluoride-safe water supply schemes built in FSB areas; B: the 34 relationships between fluoride concentration in urine of adult and fluoride concentration in drinking-water in http://bmjopen.bmj.com/ 35 FNB areas, as well as the period of fluoride reducing schemes carried out in FSB areas. 36 79x60mm (300 x 300 DPI) 37 38 39 40 41 42 43 on September 23, 2021 by guest. Protected copyright. 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from Page 34 of 36 projects projects Subjects covered by by covered Shanxi, , , projects projects Villages 1.2mg/L (n) (n) 1.2mg/L covered by by covered 7 7 7 3406 22 22 43 17393 (n) (n) 327 327 405 329896 1750 1750 4735 3764 6608 1813751 6833883 6841 10827 8998329 Water fluoride concentration >concentration fluorideWater Projects Projects FSB areas FSB Beijing, Tianjin,Beijing, Hebei : projects projects Subjects covered by by covered Whole (n) Whole projects projects Villages Villages covered by by covered (n) (n) 132 132 273 393526 1234 1234 3434 3608548 4831 4831 6586 6411339 12304 12304 28556 31082 37815 17578511 40413349 47057 79190 68405273 Projects 1 1 Subjects BMJ Open 1.2mg/L (n) (n) 1.2mg/L 80 80 97 96015 62308 4414 4414 3235747 Water fluorideWater http://bmjopen.bmj.com/ 11083 11083 4417891 25194 25194 22491430 40868 30303391 concentration >concentration Villages FNB areas FNB Subjects Whole (n) Whole 2mg/L) in drinking-water in those villages where fluoride-safe piped drinking water supply had or or supply had water drinking fluoride-safe piped where villages those in drinking-water in 2mg/L) 454 454 977 797083 829920 · 8384 8384 6867018 29259 29259 16141145 112911 112911 102483543 151985 151985 127118709 Villages on September 23, 2021 by guest. Protected copyright. subjects For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml 87 87 99421 1.2mg/L (n) (n) 1.2mg/L 140 140 79701 4819 4819 3565643 Water fluoride fluoride Water 14847 14847 6231642 31802 29325313 51695 39301720 concentration >concentration Villages Northwest: Northwest: Inner Xinjiang,Mongolia,Qinghai, Ningxia, Gansu, Shaanxi; Central For peer review only FNB and FSB areas areas and FNB FSB Whole (n) Whole villages villages subjects 6 6 8 60341 3 150726 33719656 7 142896892 727 4411 1190609 4438468 3 3 14970 13278357 27 27 231175 195523982 A nationwide screening of high fluoride ( > 1 > ( fluoride high of screening nationwide A not provided was carried out from 2005 to 2007 in 231 175 villages in 27 provinces all all over China. provinces in 27 175 villages in 231 from 2005 to 2007 out carried was not provided Supplementary material: Supplementary part of Introduction. in mentioned the were 1 in table The data Total Total South South Areas Areas Provinces Central Northeast Northwest Northwest Southwest Southwest Table 1 Screening of high fluoride water source and state of fluoride-safe water supply project in 2005-2007 in 2005-2007 water project supply of fluoride-safe state and fluoride source high water Table of Screening 1 Northeast: Heilongjiang,Northeast: Jilin, Liaoning; Shandong, Henan, Southwest:Anhui, Jiangsu; Sichuan, Chongqing and Yunnan; South: Hubei, Zhejiang, Hunan, Jiangxi,and Fujian, Guangxi Guangdong. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 35 of 36 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies 3 Item 4 No Recommendation 5 Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract 6 7 (b) Provide in the abstract an informative and balanced summary of what was done 8 and what was found 9 Introduction 10 11 Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 12 Objectives 3 State specific objectives, including any prespecified hypotheses 13 Methods 14 15 Study design For4 peer Present key elements review of study design early inonly the paper 16 Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, 17 exposure, follow-up, and data collection 18 Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of 19 participants 20 21 Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect 22 modifiers. Give diagnostic criteria, if applicable 23 Data sources/ 8* For each variable of interest, give sources of data and details of methods of 24 measurement assessment (measurement). Describe comparability of assessment methods if there is 25 26 more than one group 27 Bias 9 Describe any efforts to address potential sources of bias 28 Study size 10 Explain how the study size was arrived at 29 Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, 30 31 describe which groupings were chosen and why 32 Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 33 (b) Describe any methods used to examine subgroups and interactions 34 (c) Explain how missing data were addressed http://bmjopen.bmj.com/ 35 d 36 ( ) If applicable, describe analytical methods taking account of sampling strategy 37 (e) Describe any sensitivity analyses 38 Results 39 40 Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially 41 eligible, examined for eligibility, confirmed eligible, included in the study, 42 completing follow-up, and analysed on September 23, 2021 by guest. Protected copyright. 43 (b) Give reasons for non-participation at each stage 44 (c) Consider use of a flow diagram 45 46 Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and 47 information on exposures and potential confounders 48 (b) Indicate number of participants with missing data for each variable of interest 49 Outcome data 15* Report numbers of outcome events or summary measures 50 51 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and 52 their precision (eg, 95% confidence interval). Make clear which confounders were 53 adjusted for and why they were included 54 (b) Report category boundaries when continuous variables were categorized 55 c 56 ( ) If relevant, consider translating estimates of relative risk into absolute risk for a 57 meaningful time period 58 Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and 59 sensitivity analyses 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml1 BMJ Open Page 36 of 36 BMJ Open: first published as 10.1136/bmjopen-2012-001564 on 25 September 2012. Downloaded from 1 2 Discussion 3 Key results 18 Summarise key results with reference to study objectives 4 5 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or 6 imprecision. Discuss both direction and magnitude of any potential bias 7 Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, 8 multiplicity of analyses, results from similar studies, and other relevant evidence 9 10 Generalisability 21 Discuss the generalisability (external validity) of the study results 11 Other information 12 Funding 22 Give the source of funding and the role of the funders for the present study and, if 13 applicable, for the original study on which the present article is based 14 15 For peer review only 16 *Give information separately for exposed and unexposed groups. 17 18 Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and 19 20 published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely 21 available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at 22 http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is 23 available at www.strobe-statement.org. 24 25 26 27 28 29 Dear Editor: 30 31 We tried our best to finish the requirement of Checklist of items in our manuscript “Effects of 32 Fluoride-safe Water Supply on the Prevalence of Fluorosis in China”. 33 34 http://bmjopen.bmj.com/ 35 36 Thanks very much for your attention to our paper. 37 38 39 40 Sincerely yours，，， 41 42 Dian-jun Sun on September 23, 2021 by guest. Protected copyright. 43 44 The Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, 45 Harbin Medical University, Key Lab of Etiologic Epidemiology, Harbin Medical University, 46 Ministry of Health & Education Bureau of Heilongjiang Province; 157 Baojian Road, 47 Nangang District, Harbin Medical University, Harbin, Heilongjiang Province 150081. 48 Telephone: +86 0451 87502695; fax: +86 0451 86676184; e-mail: [email protected]. 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml2